Regulating the immune response to carbon tetrachloride-induced liver fibrosis in mice by blocking inducible co-stimulatory molecules and interleukin-33 / 中华肝脏病杂志

Objective: To investigate the effects of combined blockade of interleukin-33 (IL-33) and inducible co-stimulatory molecule (ICOS) on carbon tetrachloride-induced chronic liver fibrosis and imbalance of T helper lymphocyte subsets in mice. Methods: There were 40 BALB/c mice in each model and control group. Flow cytometry was used to determine the proportion of Th1/Th2/Th17 cells in the splenic lymphocyte suspension of mice, the expression levels of interferon γ, IL-4, and IL-17 in the splenic lymphocyte suspension of liver fibrosis mice after combined blockade of IL-33 and ICOS, and the pathological changes of liver histopathology in mice with liver fibrosis. Two independent sample t-test was used to compare data between groups. Results: Compared with the non-blocking group, the proportion of Th2 and Th17 cells in the IL-33/ICOS blocking group was significantly down-regulated (Th2: 65.96% ± 6.04% vs. 49.09% ± 7.03%; Th17: 19.17% ± 4.03% vs. 9.56% ± 2.03%), while the proportion of Th1 cells and Th1/Th2 ratio were up-regulated (Th1: 17.14% ± 3.02% vs. 31.93% ± 5.02%; Th1/Th2: 0.28 ± 0.06 vs. 0.62 ± 0.23), and the difference was statistically significant (t = 5.15, 6.03, 7.14, 4.28, respectively, with P < 0.05). After entering the chronic inflammation stage of liver fibrosis in mice (10 weeks), compared with the non-blocking group, the expression levels of IL-4 and IL-17 in the blockade group were significantly down-regulated [IL-4: (84.75 ± 14.35) pg/ ml vs. (77.88 ± 19.61) pg/ml; IL-17: (72.38 ± 15.13) pg/ml vs. (36.38 ± 8.65) pg/ml], while the expression of interferon γ was up-regulated [(37.25 ± 11.51) pg/ml vs. (77.88 ± 19.61) pg/ml], and the difference was statistically significant (t: IL-4: 4.71; IL-17: 5.84; interferon γ: 5.05, respectively, with P < 0.05). Liver histopathological results showed that hepatic necrosis, hepatic lobular structural disorder, and fibrous tissue hyperplasia were significantly lower in the blockade group than those in the non-blocking group at 13 weeks of liver fibrosis. Conclusion: Combined blockade of the ICOS signaling pathway and IL-33 can regulate Th2 and Th17 polarization, down-regulate the inflammatory response, and inhibit or prevent the occurrence and progression of fibrosis.

Changes of T cell subsets in major immune organs during sepsis / 中国小儿急救医学

Objective:To explore the changes in the proportion and number of T cell subsets in different immune organs during sepsis.Methods:Eight-week-old female C57BL/6 mice were randomly divided into sepsis group and sham group.The experimental sepsis model was constructed through cecal ligation and puncture, and the sham group just underwent sham operation.Then we detected the changes in the total number of lymphocytes and in the ratio and absolute number of CD4 + T cells, CD8 + T cells, CD4 + CD25 high Foxp3 + regulatory T cells(Treg) and CD4 + CD25 low Foxp3 - effector T cells(Teff) in the mouse spleen, axillary and inguinal lymph nodes and bone marrow by cell counting and flow cytometry 24 h and 16 d after modeling. Results:In the spleens of septic mice, the ratio and absolute numbers of CD4 + T cells and Teff, as well as the absolute number of CD8 + T cells were significantly reduced 24 h and 16 d after modeling.There was no significant change in the number of Treg 24 h after modeling, but a significant increase occurred 16 d after modeling.During sepsis, the changes of CD4 + T cells, CD8 + T cells and Teff in mouse lymph nodes were basically the same as those in the spleen; but the changes in Treg were different, with no significant change in the early stage and a significant decrease in the late stage.In addition, the absolute numbers of CD4 + T cells, CD8 + T cells, and Teff in the bone marrow did not change significantly in the 24 h model, but decreased significantly in the 16 d model.The proportion and absolute number of Treg during sepsis were significantly reduced. Conclusion:During different periods of sepsis, there is a large consumption of lymphocytes in the spleen, lymph nodes and bone marrow.In most cases, the trend of Treg changes is inconsistent or even opposite to that of other T cell subsets.There are differences in the changes of T cells among major immune organs, suggesting that the responses of different immune organs to sepsis are heterogeneous.

Research progress on OX40/OX40L axis mediated T cell immunity in the course of oral lichen planus / 口腔疾病防治

@#Oral lichen planus (OLP) is a common chronic disease of the oral mucosa with unclear pathogenesis. Local infiltration of T cells plays a key role in the pathological process of OLP. Increased evidence supports the notion that the imbalance of helper T cells (Th) 1/Th2 and Th17/regulatory T cells (Treg) and their related cytokines is closely related to the pathogenesis and progression of OLP. In recent years, studies have shown that OX40 (CD134) and its ligand OX40L (CD252) play an important role in the process of the T-cell immune response. They participate in the balance regulation of Th1/Th2 and Th17/Treg, mediate the imbalance of pro-inflammatory and anti-inflammatory, and affect the occurrence and development of a variety of autoimmune diseases. However, there is no direct evidence that the OX40/OX40L axis mediates the imbalance of T-cell subsets in the pathogenesis of OLP. Therefore, large sample clinical as well as in vitro and in vivo experimental studies on the mechanism by which the OX40/OX40L axis regulates the balance of T-cell subsets in OLP are still needed in the future.

Immune reconstitution in patients with allogeneic hematopoietic stem cell transplantation after CAR-T immunotherapy / 中华检验医学杂志

Objective:To study the performance of immune reconstitution in patients with chimeric antigen receptor (CAR)-T cell immunotherapy bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 61 patients with acute B lymphocytic leukemia (B-ALL) who received CAR-T cell bridging allo-HSCT in Beijing Lu Daopei Hospital from August 2018 to December 2021 were enrolled, and the clinical medical records of the above patients were retrospectively analyzed. The average age was 14 (7, 30) years old, including 39 males and 22 females. 32 patients were treated with CAR-T cell immunotherapy(CAR-T Group) and 29 didn't with CAR-T cell immunotherapy(non-CAR-T group). The follow-up period was 561 (235,784) days. Multicolor flow cytometry was used to detect the peripheral blood lymphocyte subsets, i.e. total lymphocytes, T lymphocytes, helper T cells, cytotoxic T cells, B lymphocytes, NK cells, and Treg cell counts before transplantation and 1, 2, 3, 6, 8, 10, and 12 months after transplantation, to evaluate the immune reconstitution performance post allo-HSCT.Results:Serum globulin before transplantation: The IgA level in the CAR-T group was 0.18 (0.06, 0.49) g/L, which was lower than that of 1.03 (0.63, 1.56) g/L in the non-CAR-T group ( U=103.5, P<0.001). The IgG level in the CAR-T group was 5.54 (4.04, 7.09) g/L, lower than that of 6.78 (5.27, 9.26) g/L in the non-CAR-T group, ( U=1 298.5, P=0.017), and the IgM level in the CAR-T group was 0.18 (0.05, 0.30) g/L, lower than that of 0.40 (0.26, 0.71) g/L in the non-CAR-T group ( U=166.0, P<0.001). In the CAR-T group before transplantation, the absolute count of total lymphocyte in peripheral blood was 833.00 (335.00, 1 727.50) /μl, lower than that of 1 052.00 (545.75, 1 812.50) /μl in the non-CAR-T group ( U=404.0, P<0.001). The absolute count of T lymphocyte in the CAR-T group before transplantation was 686.00 (233.00, 1 307.00)/μl, lower than that of 860.00 (391.00, 1 419.75) /μl in the non-CAR-T group ( U=406.0, P<0.001). The absolute count of helper T lymphocytes in the CAR-T group was 146.00 (40.50, 327.50) /μl, lower than that of 162.50 (66.00, 384.75) /μl in the non-CAR-T group ( U=494.0, P=0.002). The absolute count of cytotoxic T lymphocytes in the CAR-T group was 343.00 (56.50, 924.00) /μl, lower than that of 478.00 (143.50, 992.25) /μl in the non-CAR-T group ( U=483.5, P=0.001). The absolute count of B lymphocytes in CAR-T group was 22.00 (6.00, 186.00) /μl, lower than that of 33.00 (8.00, 220.00) /μl in the non-CAR-T group ( U=498.0, P=0.002). And when two groups of patients were monitored after transplantation, there was no statistical difference in absolute cell counts of each immune cell subpopulation( P>0.05). Comparing the clinical features of the two groups, the pre-transplant history of the CAR-T group was 981.00 (368.50, 1 514.75) d, longer than that of 323.00 (167.50, 450.50) d in the non-CAR-T group ( U=263.0, P=0.004). The dose of rabbit anti-human thymic immunoglobulin (ATG) in the pretreatment protocol of patients in the CAR-T group was 5.00 (5.00, 7.50) mg/Kg, lower than that of 7.00 (5.00, 7.50) mg/kg in the non-CAR-T group ( U=288.5, P=0.018). The infusion dose of CD34 +cells in the CAR-T group was 5.91 (4.23, 6.02) ×10 6/kg, higher than that of 4.51 (4.00, 5.93)×10 6/kg in the non-CAR-T group ( U=291.0, P=0.012). The duration of the application of cyclosporine after transplantation in the CAR-T group was 167.00 (119.25, 299.50) d, which was shorter than that of 197.00 (102.50, 450.50) d in the non-CAR-T group ( U=421.0, P=0.001). Conclusions:For patients in CAR-T group with low immune function before transplantation, it may be possible to make them comparable to non-CAR-T group in immune reconstitution state by reducing the dose of pretreatment ATG, increasing the counts of CD34 + cells infusion in the graft, and discontinuing cyclosporine as soon as possible after transplantation.

Regulation Effect and Clinical Efficacy of Addition and Subtraction Therapy of Jinkui Shenqiwan Combined with Buzhong Yiqitang on Immune Inflammatory Factors of Patients with Postmenopausal Osteoporosis and Deficiency of Spleen and Kidney / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of addition and subtraction therapy of Jinkui Shenqiwan combined with Buzhong Yiqitang to postmenopausal osteoporosis （PMO） with deficiency of spleen and kidney， and to investigate its regulation effect on immune inflammatory factors. Method:One hundred and sixty patients were randomly divided into observation group and control group， with 80 cases in each group. Both groups got comprehensive western medicine treatment measures. Patients in control group additionally got Zhuanggu Zhitong capsule， 4 capsules/time， 3 times/day. Patients in observation group additionally got addition and subtraction therapy of Jinkui Shenqiwan combined with Buzhong Yiqitang， 1 dose/day. The treatment was continued for 24 weeks. Before and after treatment， lumbar L2-4 bone mineral density （BMD） was detected by Dual energy X-ray absorptiometry （DXA） and lumbar BMD was detected by quantitative CT （QCT）. Scores of traditional Chinese medicine（TCM） syndromes and Chinese osteoporosis-targeted quality of life questionnaire （COQOL） were graded. Levels of Estradiol （E₂）， type Ⅰ procollagen amino terminal pro peptide （PINP）， serum osteocalcin （OC）， osteoprotegerin （OPG）， type Ⅰ collagen cross-linked C-terminal peptide （S-CTX）， tartrate resistant acid phosphatase （TRACP） and urinary pyridinoline （PYD） were detected. Levels of CD4⁺ T cells， CD8⁺ T cells， interleukin-17 （IL-17）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， <italic>γ-</italic>interferon（IFN-<italic>γ</italic>） and interleukin-4 （IL-4） were calculated. The proportion of T helper cell （Th）17 and regulatory T cell （Treg） in CD4⁺ T cells was calculated. Besides， the safety was evaluated. Result:Bone density was detected by DXA in observation group， and its T-value and bone density detected by QCT were all higher than those in control group （<italic>P</italic><0.01）. After treatment， scores of TCM syndrome and COQOL were lower than those in control group （<italic>P</italic><0.01）. Levels of PINP， OC， S-CTX， TRACP and PYD/Cr were all lower than those in control group （<italic>P</italic><0.01）. Levels of OPG， CD8⁺ and Treg were higher than those in control group （<italic>P</italic><0.05）， levels of Th17， Th17/Treg， CD4⁺/CD8⁺， IL-17， TNF-<italic>α</italic> and IFN-<italic>γ </italic>were lower （<italic>P</italic><0.01）， and levels of IL-4 and E₂ were higher than those in control group （<italic>P</italic><0.01）. The clinical efficacy in observation group was better than that in control group （<italic>Z</italic>=2.103， <italic>P</italic><0.05）. Conclusion:On the basis of calcium and vitamin D supplementation， Jinkui Shenqiwan combined with Buzhong Yiqitang can improve levels of E₂ and bone density， reduce clinical symptoms， improve quality of life， regulate bone metabolism index and immune inflammation reaction， with better clinical efficacy and safety.

Preventive and therapeutic effects and mechanism of Xiaoer Feike Granules on chronic bronchitis induced by lipopolysaccharide in rats / 中国中药杂志

The aim of this paper was to investigate the preventive and therapeutic effects of Xiaoer Feike Granules(XEFK) on chronic bronchitis in rats and its mechanism. Except for 10 rats in the blank group, the remaining 50 of the 60 SD rats were used to establish a model of chronic bronchitis induced by LPS. On the 22 nd day, the model rats were randomly divided into 5 groups according to their body weight, and administrated with purified water, Keteling Capsules 0.11 g·kg~(-1), XEFK 3.2, 1.6 and 0.8 g·kg~(-1)(the dosing concentrations were 0.32, 0.16, 0.08 g·mL~(-1), respectively). These rats took the corresponding drug orally once a day, for consecutive 21 days. The rats were anesthetized 1 hour after the last administration, and the lavage bronchus and alveoli were collected. Then, after the fixation of the smear, neutrophils were counted microscopically, and the contents of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) in the bronchoalveolar lavage fluid(BALF) were detected by colorimetric method. Flow cytometry was used to detect the content changes of T cell subsets CD4~+, CD8~+, CD4~+/CD8~(+ )in serum. Hemorheology related indexes were detected by automatic hemorheology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-2, IL-6 and IL-10 in serum. The expression of TNF-α and IL-10 mRNA in lung was detected by Real-time quantitative PCR(RT-qPCR). HE staining was used to observe the pathological changes in the bronchitis tissues. Compared with the model group, XEFK high and medium dose groups could significantly reduce the contents of neutrophils and MDA in bronchial lavage fluid, and increase the activities of GSH-Px and SOD in BALF, and repair the chronic inflammatory cell infiltration and lymphoid tissue hyperplasia in the bronchial mucosal layer and submucosal layer. The high-dose group could reduce the plasma viscosity of rats, but there was no statistical difference in other hemorheological indexes. CD4~+, CD8~+, CD4~+/CD8~+, IL-2 and IL-10 contents in each dose group were significantly increased, and TNF-α, IL-1β and IL-6 contents were significantly decreased in serum. Each dose group could significantly down-regulate the expression level of TNF-α mRNA in the lung and increase the expression of IL-10 mRNA. XEFK could reduce lipid peroxidation, increase the content of peripheral blood T cell subsets, regulate the release and secretion of inflammatory factors, and repair the morphological and pathological changes of bronchial tissue. Its mechanism might be related to the improvement of inflammatory response and the enhancement of immune function.

Regulatory Effect of Huaihuasan Combined with Taohuatang on Immune Inflammation During Active Period of Ulcerative Colitis with Cold-heat Syndrome / 中国实验方剂学杂志

Objective::To observe effect of addition and subtraction therapy of Huaihuasan combined with Taohuatang to ulcerative colitis with cold-heat complicated syndrome at active stage, and to study regulation effect to immune function and inflammatory response. Method::One hundred and twelve patients were randomly divided into control group and observation group by random number table. Patients with light and middle symptoms in control group got mesalazine slow release tablets, 1.0 g/time, 3 times/days, patients with severe symptoms or whose symptoms were not changed after getting for 4 weeks in control group got prednisone acetate tablets, 0.75 mg·kg-1·d-1 for 3 times. Based on the treatment in control group, patients in observation group added Huaihuasan combined with Taohuatang, 1 dose/day. The course of treatment was 4 weeks. At remission period, mesalazine slow release tablets were used for maintain long-term maintenance therapy, 0.5 g/times, 3 times/days. Scores of disease activities were graded by improvement mayo, and clinical remission and clinical efficacy were recorded, scores of cold-heat complicated syndrome, mucous membrane under enteroscopy and histology of mucosa belongs to Geboes were graded. And levels of tumor necrosis factor-α(TNF-α) in peripheral blood, interleukin-8 (IL-8), IL-10, T lymphocyte subsets (CD4+, CD8+), and adverse reactions, 6 months' follow-up and recurrence were also be recorded. Result::Therapeutic effect of traditional Chinese medicine syndromes were analyzed by rank sum test, which in observation group was better than that in control group (Z=1.915, P<0.05). Clinical effect in observation group was 98.04%(50/51) higher than 84.00%(42/50) in control group, clinical remission rate was 94.12%(48/51) higher than 78.00%(39/50) in control group, and mucosal healing rate was 96.08%(49/51) higher than 82.00%(41/50) in control group (P<0.05). Scores of mayo, cold-heat complicated syndrome, colonic mucosa and index scores of Geboes were all lower than those in control group (P<0.01). And levels of TNF-α, IL-8 and CD8+ were lower than those in control group (P<0.01), and levels of IL-10, CD4+ and CD4+ /CD8+ were higher than those in control group (P<0.01). Recurrence rate during 6 months in observation group was 10.42%(5/48) lower than 30.77%(12/39) in control group (χ2=5.669, P<0.05), as for adverse reactions, there was no significant difference between two groups. Conclusion::Huaihuasan combined with Taohuatang can induce UC to remission period, inhibit the activity of disease, alleviate clinical symptoms, regulate immune function and expression of inflammatory factors, alleviate inflammatory reaction, promote intestinal mucosal healing, and can maintain clinical remission and reduce recurrence. The clinical efficacy is superior to that of 5-ASA/glucocorticoid in Western medicine.

Effect of Wenjing Huayu Zhitong Therapy in Treating Primary Dysmenorrhea and Its Regulatory Mechanisms on T Cell Subsets / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Wenjing Huayu Zhitong therapy in treating primary dysmenorrhea (PD) with cold coagulation and blood stasis, and to explore its immune mechanisms on PD. Method:The 108 PD patients with cold coagulation and blood stasis syndrome were collected and randomly divided into traditional Chinese medicine (TCM) group, ibuprofen group and placebo group according to the random number table method, with 36 cases in each group. All patients received corresponding medicines three days before menstruation. The patients in TCM group were treated with TCM and ibuprofen sustained release capsule simulator. The patients in ibuprofen group were treated with ibuprofen sustained-release capsule and TCM simulator. The patients in placebo group were treated with TCM simulator and ibuprofen sustained-release capsule simulator. Treatment lasted for 6 consecutive days for three menstrual cycles, and follow-up was conducted for three menstrual cycles after drug withdrawal. The visual analogue score (VAS), total time of abdominal pain and TCM symptom scores in each menstrual cycle were recorded. The levels of CD3+, CD4+, CD8+ and the ratio of CD4+/CD8+ in peripheral blood before and after treatment were detected by flow cytometry. Result:After treatment for three menstrual cycles, both the TCM group and ibuprofen group were better than placebo group in reducing VAS score and reducing total abdominal pain time (P<0.01). The long-term follow-up effect after drug withdrawal in TCM group was significantly better than that in ibuprofen group (P<0.01). The total effective rate was 91.43% (32/35) in TCM group, 66.67% (10/33) in ibuprofen groups, and 30.30% (10/33) in placebo group . The efficacy of the TCM group was better than that of the ibuprofen group (χ2=-2.971, P<0.01), and the efficacy of the ibuprofen group was better than that of the placebo group (χ2=-2.371, P<0.05). After treatment, the levels of CD3+, CD4+ and CD4+/CD8+ in TCM group were significantly increased and the levels of CD8+ were decreased significantly as compared with those before treatment (P<0.01). After treatment, the levels of CD4+ and CD4+/CD8+ in TCM group were higher (P<0.05，P<0.01)，while the levels of CD8+ were significantly lower than those in ibuprofen group and placebo group (P<0.01). Conclusion:Wenjing Huayu Zhitong therapy can reduce the VAS score and accumulative time of abdominal pain, and improve the dysmenorrhea symptoms in patients with PD. Reversal of the T cell subsets disorder may be one of its mechanisms in treating PD with cold coagulation and blood stasis.

Effects of BCG polysaccharide nucleotides combined with Tripterygium wilfordii polyglycosides on inflammatory factors and T cell subsets in patients with chronic urticaria / 中国基层医药

Objective To study the effect of BCG polysaccharide nucleic acid combined with Tripterygium wilfordii polyglycoside(TWP) on inflammatory factors and T cell subsets in patients with chronic urticaria. Methods From January 2015 to January 2017,84 patients of chronic urticaria in Gujiao Central Hospital were selected in the research. The patients were randomly divided into observation group and control group,with 42 cases in each group. The control group was treated with conventional therapy,and the observation group was treated with BCG polysaccharide nucleic acid combined with TWP. The levels of IL－2,IL－4,IL－10,peripheral blood interferon－γ(IFN－γ),T cell subsets ( CD+4, CD+8, CD+4/CD+8) were observed, and the clinical efficacy was compared. Results After treatment,the total effective rate of the observation group was higher than that of the control group[41(97. 62% ) vs. 36(85. 71% )](χ2=3. 896,P＜0. 05). The levels of IL－2 and IFN－γ in the observation group were higher than thoseinthecontrolgroup[(314.54±45.47)ng/Lvs.(285.04±46.84)ng/L,(310.25±32.80)ng/Lvs.(265.14± 28. 11)ng/L](t=2. 928,6. 767,all P＜0. 05). The levels of IL－4 and IL－10 in the observation group were lower thanthoseinthecontrolgroup[(18.65±3.14)ng/Lvs.(26.09±4.52)ng/L,(57.65±6.34)ng/Lvs.(63.74± 6. 82)ng/L](t=8. 760,4. 238,all P＜0. 05). The levels of CD+4,CD+4/CD+8in the observation group were higher thanthoseinthecontrolgroup[(39.86±6.96)% vs.(34.44±7.06)%,(1.60±0.14) vs.(1.34±0.15)](t=3. 543,8. 212,all P＜0. 05). The level of CD+8in the observation group was lower than that in the control group [(24.34±3.99)% vs.(27.24±4.33)%](t=3.191,P＜0.05).Conclusion BCG polysaccharide nucleic acid combined with TWP in the treatment of chronic urticaria can effectively increase peripheral blood IFN－γ and IL－2 levels,decrease IL－4,IL－10 levels,improve levels of inflammatory cytokines and T cell subsets( CD+4,CD+8and CD+4/CD+8),the efficacy is safe and reliable,it is worthy of application and promotion.

Analysis of B cell subsets in rhumatoid arthritis patients and the effect of epigallocatechingallate on B cell subsets / 上海交通大学学报（医学版）

Objective:To explore the characteristics of B cell subsets in rheumatoid arthritis (RA) patients and the regulation of epigallocatechingallate (EGCG) on B cell subsets in RA patients. Methods:Twenty-nine age- and sex-matched RA patients and 29 healthy controls were selected, and the difference of B cell subsets in peripheral blood between the two groups was analyzed by paired t-test. According to the value of disease activity score in 28 joints (DAS28), RA patients were divided into active group (2.6 ≤ DAS28 0.05). There was no significant difference in the numbers and the proportions of total B cells and B cell subsets (except CD19+ IL-10+ Breg) between 10 RA patients of active group and 19 RA patients of highly active group (P>0.05). There was no significant difference in the number and the proportion of CD19+ IL-10+ Breg in lymphocytes between 6 RA patients of active group and 12 RA patients of highly active group (P>0.05). The proportion of total B cells was weakly positively correlated with IgG type rheumatoid factor (r=0.308). EGCG could significantly increase the proportion of CD19+ IL-10+ Breg (P0.05). Conclusion:B cells may play an auxiliary role in the development of RA. The number of CD19+ IL-10+ Breg in RA patients increases as a feedback. EGCG can promote Breg proliferation and suppress BAFF-R mRNA expression.

Advances in the study of T cell immunity in invasive fungal infections secondary to sepsis / 上海交通大学学报（医学版）

Invasive fungal infections (IFI) has high morbidity and mortality. It is more common in hospital infections, and especially in sepsis, the risk of secondary IFI is increased. Immunosuppression of sepsis may affect immune function of T cells, and various T cells subsets have different effects on various fungal pathogens of IFI. The review discusses the pathophysiological processes, mechanism and therapeutic methods of T cell immunity in IFI secondary to sepsis, in order to summarize the role of T cells in IFI secondary to sepsis and introduce the new immunotherapy.

T cell subsets and immunoglobulin G levels are associated with the infection status of systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder that affects nearly all organs and tissues. As knowledge about the mechanism of SLE has increased, some immunosuppressive agents have become routinely used in clinical care, and infections have become one of the direct causes of mortality in SLE patients. To identify the risk factors indicative of infection in SLE patients, a case control study of our hospital's medical records between 2011 and 2013 was performed. We reviewed the records of 117 SLE patients with infection and 61 SLE patients without infection. Changes in the levels of T cell subsets, immunoglobulin G (IgG), complement C3, complement C4, globulin, and anti-double-stranded DNA (anti-ds-DNA) were detected. CD4+ and CD4+/CD8+ T cell levels were significantly lower and CD8+ T cell levels were significantly greater in SLE patients with infection than in SLE patients without infection. Additionally, the concentrations of IgG in SLE patients with infection were significantly lower than those in SLE patients without infection. However, complement C3, complement C4, globulin, and anti-ds-DNA levels were not significantly different in SLE patients with and without infection. Therefore, clinical testing for T cell subsets and IgG is potentially useful for identifying the presence of infection in SLE patients and for distinguishing a lupus flare from an acute infection.

Current situation and challenges of T cell receptor-engineered T cells in anti-tumor therapy / 中国肿瘤生物治疗杂志

@#T cell receptor-engineered T cell (TCR-T) therapy is one of the hotspots in the field of cancer immunotherapy. Considerable achievements have been made since the first successful clinical trial in 2006. However, problems still remain in cytotoxicity, safety and persistence of TCR-T therapy despite the rapid development. Improving the immunosuppressive tumor microenvironment and enhancingchemotaxis, infiltration as well as activation of TCR-T cell will be the key to improve its anti-tumor effect. Neoantigens, which are highly tumor-specific and immunogenic,are the basis for safe and effective treatment and individualized cancer immunotherapy. Besides, infusion of less differentiated T cell subsets is also a reliable way to generate a long-lasting immune response. Here, combing with current research progress, we offer our perspectives on the current situation and challenges of TCR-T from the three aspects above.

Differences in susceptibility to Lewis lung carcinoma and T lymphocyte subsets of aged mice / 中华老年医学杂志

Objective To investigate the differences in susceptibility to Lewis lung carcinoma and T lymphocyte subsets in the immune microenvironment between young and elderly mice.Methods Six C57/B6 mice at two months(young)and six mice at twelve months(aged)were injected with Lewis lung carcinoma cells at the dose of 1 × 106 in the left armpit to establish a murine model of lung carcinoma.The weight and tumor growth were monitored.Blood samples for routine blood tests were collected after 24 days.The proportions of CD4+ and CD8+T cells in the spleen were detected by flow cytometry,and the infiltration of CD4+,CD8+ T cells and related effector T cells in the tumor microenvironment were determined in the same way.Results The body weight of tumor bearing mice in the aged group was significantly higher than that in the young group(P ＜0.001);The tumor weight in the aged group(5.084±0.528)g was significantly higher than that in the young group(2.963 ±0.378)g(t =3,349,P =0.012);Routine blood tests showed that the numbers of leukocytes and subsets(except mononuclear)in the aged group were significantly lower than in the young group(P ＜0.05);Flow cytometry found that the effector and memory/effector CD4+T cell ratios in the spleen were significantly higher in the aged group than in the young group(P ＜0.001)and the expression of effector and memory/effector CD8+T cells in the tumor microenvironment was also significantly higher than in the young group(P ＜0.05);Quantitative expression values of IL-6 and IL-10 in the tumor microenvironment were 25090±3820 and 10670± 1793 in the aged group and 6252±864 and 3061±451 in the young group,respectively.Moreover,the expression levels of IL-6 and IL-10(t =3.925,P =0.01;t =3.552,P =0.02)in the tumor microenvironment in the aged group were significantly lower than those in the young group.Conclusions Young mice are more susceptible to Lewis lung carcinoma,probably as a result of differences in inflammation and immunity.

Correction study of ketogenic diet adjustment for balance of peripheral blood helper T cell subsets in children with refractory epilepsy / 中华实用儿科临床杂志

Objective To research ketogenic diet(KD) adjustment for the balance of helper T cell subsets in peripheral blood of children with refractory epilepsy (CRE).Methods Forty-two CRE children admitted to Children's Hospital Affiliated to Zhengzhou University from January 2015 to May 2016 were retrospectively analyzed.All the CRE patients were treated with KD,and the data before and after treatment were collected.During the same period,40 healthy children were taken as the healthy control group.The changes of the compositions of helper T cells 17(Thl7),regulatory T cells (Treg) and helper T cells 1 (Th1) in each group were recorded.Meanwhile,m RNA expression of Th17,Treg and Th1 related factors were detected,and plasma levels of inflammatory cytokines were analyzed before and after treatment.Results There were less Treg cells [(1.75 ± 0.53) ％] in children with CRE compared with the healthy control group [(3.97 ± 0.28)％],but more Th1[(12.25 ± 1.03)％] and Th17 cells [(2.89 ±0.68)％]compared with the healthy control group [(7.75 ± 2.42) ％,(1.86 ± 0.57) ％] (t =23.542,11.049,7.415,all P ＜0.05).The mRNA expression of interleukin-17A (IL-17A),gamma-interferon (IFN-γ),in the CRE group before treatment [(2.46 ± 0.75) × 10-4,(1.48 ± 0.64) × 10-2],were significantly higher than those in the healthy control group [(0.91 ±0.24) × 10-4,(0.47 ±0.11) × 10-2].The mRNA expression levels of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and tumor necrosis factor receptor (GITR) in the pre-treatment group of CRE children[(20.02 ± 6.57) × 10-2;(12.42 ± 6.46) × 10-5] were significantly lower than the healthy control group [(26.57 ± 6.75) × 10-2;(16.31 ± 4.18) × 10-5];the difference was statistically significant (F =4.697,5.232,4.981,3.872,all P ＜ 0.05).After treatment,mRNA expression levels of IL-17A [(1.20 ± 0.44) × 10-4],IFN-γ[(0.7 ±0.41) × 10-2],CTLA-4 [(10.72 ±2.99) × 10-2] and GITR [(6.04 ±2.51) × 10-5] were significantly decreased compared with the level of pre-treatment group [(2.46 ± 0.75) × 10-4,(1.48 ± 0.64) × 10-2,(20.02 ±6.57) × 1 0-2,(12.42 ± 6.46) × 10-5,p ＜ 0.05].The levels of IL-17 A,IFN-γ,Cyclooxygenases-2 (COX-2)and Prostaglandin F2α (PGF2α) in children with CRE the level of pre-treatment group [(26.52 ± 6.17) ng/L,(11.19 ± 3.15) ng/L,(2.14 ± 1.31) ng/L,(205.74 ± 32.30) ng/L] were significantly higher than those in the healthy control group [(13.93 ± 2.98) ng/L,(8.87 ± 1.09) ng/L,(1.04 ± 0.33) ng/L,(109.80 ± 38.74) ng/L](F=5.361,3.987,3.654,11.370,all P ＜ 0.05).The levels of IL-17A [(18.48 ± 6.18) ng/L],IFN-γ[(9.54±1.42) ng/L],COX-2 [(1.46 ±0.72) ng/L] and PGF2α[(126.13±13.07) ng/L]in CRE children were reduced after KD adjustment [(26.52 ± 6.17) ng/L,(1 1.19 ± 3.15) ng/L,(2.14 ± 1.31) ng/L,(205.74 ±32.30) ng/L],and the differences were statistically significant (all P ＜ 0.05).Conclusions KD adjustment may have a beneficial effect on balance of peripheral blood in children with CRE.KD adjustment is positively correlated with the level of factors related to Th cells and inflammatory cytokines.

Analysis of Peripheral B Cell Subsets in Patients With Allergic Rhinitis

PURPOSE: Recent evidence suggests that B cells can both promote and inhibit the development and progression of allergic disease. However, the characteristics of B cell subsets in patients with allergic rhinitis (AR) have not been well documented. This study aimed to analyze the characteristics of B cell subsets in the peripheral blood of AR patients. METHODS: Forty-seven AR patients and 54 healthy controls were enrolled in this study, and the B cell subsets in peripheral blood of all subjects were analyzed by flow cytometry. Moreover, the serum total immunoglobulin E (IgE) and IgE concentrations secreted into the cultured peripheral blood mononuclear cells (PBMCs) were measured by using enzyme-linked immunosorbent assay. RESULTS: We found the peripheral blood of AR patients contained higher percentages of memory B cells, plasma cells, and CD19+CD24hiCD27+ regulatory B cells (Bregs) than those of age-matched healthy controls (P < 0.05), while the percentages of naïve B cells and CD19+CD24hiCD38hi Bregs were significantly lower in AR patients than in healthy individuals (P < 0.05). In addition, the serum total IgE and IgE concentrations secreted into the cultured PBMCs were elevated in AR patients than in the healthy controls (P < 0.05). CONCLUSIONS: Our findings indicate that AR patients were characterized by increase in terminally differentiated memory B cells or plasma cells and decreases in CD19+CD24hiCD38hi Breg cells in the peripheral blood.

Immune Characterization of Bone Marrow-Derived Models of Mucosal and Connective Tissue Mast Cells

PURPOSE: It is well appreciated that mast cells (MCs) demonstrate tissue-specific imprinting, with different biochemical and functional properties between connective tissue MCs (CTMCs) and mucosal MCs (MMCs). Although in vitro systems have been developed to model these different subsets, there has been limited investigation into the functional characteristics of the 2 major MC subsets. Here, we report the immunologic characterization of 2 MCs subsets developed in vitro from bone marrow progenitors modeling MMCs and CTMCs. METHODS: We grew bone marrow for 4 weeks in the presence of transforming growth factor (TGF)-β, interleukin (IL)-9, IL-3, and stem cell factor (SCF) to generate MMCs, and IL-4, IL-3, and SCF to generate CTMCs. RESULTS: CTMCs and MMCs differed in growth rate and protease content, but their immune characteristics were remarkably similar. Both subsets responded to immunoglobulin E (IgE)-mediated activation with signaling, degranulation, and inflammatory cytokine release, although differences between subsets were noted in IL-10. CTMCs and MMCs showed a similar toll-like receptor (TLR) expression profile, dominated by expression of TLR4, TLR6, or both subsets were responsive to lipopolysaccharide (LPS), but not poly(I:C). CTMCs and MMCs express receptors for IL-33 and thymic stromal lymphopoietin (TSLP), and respond to these cytokines alone or with modified activation in response to IgE cross-linking. CONCLUSIONS: The results of this paper show the immunologic characterization of bone marrow-derived MMCs and CTMCs, providing useful protocols for in vitro modeling of MC subsets.

Clinical study of peripheral blood T cell subsets in patients with malignant lymphoma by flow cytometry / 实用肿瘤学杂志

Objective The aim of this study was to investigate the effect of flow cytometry on peripheral blood T cell subsets in patients with malignant lymphoma and its relationship with clinicopathological and tumor types.Methods Ninety-eight patients with malignant lymphoma treated in our hospital from August 2014 to September 2016 were selected as the study group.Ninety-eight healthy subjects were selected as the control group.The peripheral blood T cell subsets(CD3 +,CD4 +,CD8 +,CD4 +/CD8 +)were detected in patients and healthy controls by flow cytometry.Results The levels of CD3 +and CD4 +/CD8 +in the study group were (55.63±11.25)and(1.32±0.62),respectively,which were significantly lower than those(68.96±12.63)and (1.59±0.59)of the control group(P<0.05).The levels of CD4 +and CD8 +were(33.67±8.14)and(26.02±4.67),respectively in the study group,were no difference from the control group(34.12±8.33)and(25.67±4.53)(P>0.05).The levels of CD3+and CD4 +/CD8 +in patients with Hodgkin's lymphoma were(54.63±11.36),(1.22±0.65),respectively,and(55.52±12.02),(1.34±0.71)for non-hodgkin lymphoma.They were significantly decreoseg in the control group(68.96±12.63 for CD3 +and 1.59±0.59 for CD4 +/CD8 +) (P<0.05).The level of CD4 +and CD8 +were no difference amoupst Hodgkin's lymphoma(33.78±8.23 for CD4 +and 25.74±4.88 for CD8 +),non-Hodgkin's lymphoma(25.74±4.88 for CD4 +and 33.62±8.74 for CD8 +)and control group(34.12±8.33 for CD4 +and 25.67±4.53 for CD8 +)(P>0.05).The levels of CD3 +,CD4+and CD4 +/CD8 +in patients with Ⅲ ~Ⅳ stage malignant lymphoma were(52.66±12.47), (28.25±6.32)and(1.30±0.62),respectively,which were significantly lower than those(68.96±12.63), (34.12±8.33)and(1.59±0.59)in the control group(P<0.05).The level of CD3 +in patients with phase Ⅰ-Ⅱ malignant lymphoma(58.63±11.85)was significantly lower than that in the control group(68.96±12.63)(P<0.05).The level of CD8 +in patients with phase Ⅰ-Ⅱ malignant lymphoma(29.63±3.57)was significantly higher than that in the control group(25.67±4.53)(P<0.05).Conclusion The detection of peripheral blood T cell subsets by flow cytometry can be used as an important methods to diagnose the disease,staging and immune status of patients with malignant lymphoma,which has high application value.

Role of lupus murine B cells in abnormal development of T cell subsets / 中华风湿病学杂志

Objective To study the effects of B cells from lupus prone Triple congenic (TC) mouse model on the differentiation and development of T cell subsets. Methods The spleen size and B cell numbers were measured, and surface CD40, CD86 and Ⅰ-Ab molecules on B cells as well as CD4+T cell subsets were detected using flow cytometry when the spontaneous systemic lupus erythematosus (SLE) model TC mice and control B6 mice were 6 months old. In addition, the chimera of TC B cells and B6 CD4+T cells or chimera of B6 B cells and B6 CD4+ T cells were transferred into B6.Rag-/- mice via intravenous injection. Then, T cell subsets in the spleen of recipient B6.Rag-/-mice were observed 7 days after cell transplantation. Results TC mice had significantly bigger spleen [(5337±934) mg] and more CD19+B cell number [(276.0±48.7)×107] than control B6 mice [spleen weight: (91±4) mg; B cell number: (6.4±0.3)×107](P0.05). The recipient B6.Rag-/-mice transplanted with TC B cells had significantly more Th1 subset [(54.1±2.8)%] and IL-21+CD4+T cell population [(14.3±1.0)%], but less Th17 subset [(2.05±0.09)%] in spleen than the recipient B6.Rag-/-mice administered by B6 B cells [Th1 subset: (39.5±1.1)%; IL-21+CD4+T cell population:(7.5±1.2)%;Th17 subset:(6.45±1.10)%](P<0.01). Conclusion The B cells of lupus-prone TC mice exhibit a markedly hyper-activation in spleen, and promote CD4+T cells differentiation preferentially into Th1 subset and IL-21+CD4+T cell population, which may further contribute to SLE pathogenesis.

Clinical Observation on Brucea Javanica Oil Combined with Gemcitabine and Cisplatin in the Treatment of Advanced NSCLC / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of Brucea javanica oil combined with gemcitabine and cisplat-in in the treatment of advanced non small cell lung cancer(NSCLC). METHODS:Totally 131 advanced NSCLC patients selected from Huanggang Hospital of TCM during Feb. 2014 to Jan. 2016 were divided into observation group(71 cases)and control group (60 cases)according to random number table. Control group was given Gemcitabine for injection(1st and 8th day)+Cisplatin injec-tion (2nd day),every 21 days,twice as a treatment course. Observation group was additionally given Breucea javanica oil oral emulsion 20 mL,po,2-3 times/d,for consecutive 14 d (3 days before chemotherapy). Both groups received treatment for 87 d and followed up until Jul. 1,2016. Clinical efficacy,the levels of T cell subsets (CD3+,CD4+,CD8+),survival time were ob-served in 2 groups. Single factor and multiple factor analysis was conducted for survival time. The occurrence of ADR was record-ed. RESULTS:The total response rate of observation group (32.39%) was higher than that of control group (25.00%),without statistical significance(P>0.05). Before treatment,there was no statistical significance in the levels of CD3+,CD4+ and CD8+ be-tween 2 groups(P>0.05). After treatment,the levels of CD3+ and CD4+ in observation group were increased significantly,while CD8+ level was decreased significantly;there was statistical significance compared to control group at corresponding period (P0.05). Single factor analysis showed that the survival time of patients aged 0.05). CONCLU-SIONS:Brucea javanica oil combined with gemcitabine and cisplatin in the treatment of advanced NSCLC patients,although not significantly improve the therapeutic effect,but can significantly improve the cellular immune function. With or without pleural effu-sion and age are infuential facters for survival time of advanced NSCLC patients.