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Background: Systemic lupus erythromatosus (SLE) is an autoimmune disease with 20–65% of patients developing lupus nephritis (LN). Studies have reported 10% of LN patients will end up with end stage renal disease and their mortality rate is higher compared to patients without LN. Abnormality of regulatory T cells (Tregs) level is thought to be a potential factor for this LN development. The aim of study was to evaluate the percentage of Tregs in LN patients.Methods: This was a comparative cross sectional study involving LN patients and age and gender matched controls with a 2:1 ratio. The patients were grouped into active and inactive LN based on their lupus activity index; complement levels, ANA, dsDNA antibodies, ESR, SLE Disease Activity Index (SLEDAI2K) score and also urine PCI (uPCI>0.05 for active group). Disease history, demographic data, routine blood test, peripheral blood for differentials count were taken and recorded. Peripheral blood mononuclear cells were stained with CD4, CD25 and Foxp3 antibodies and percentage of Tregs was analysed using BD fluorescence-activated cell sorting (FACS) cytometer. We compared demographic and laboratory parameters between healthy controls and LN patients as well as active and inactive LN patients.Results: A total of 34 LN patients (32 females, 2 males) were recruited. Their mean age and disease duration were 37.97±11.14 years and 110.95±65.07 months respectively. Thirteen matched controls with mean age 35.23±7.89 years were enrolled. There was no demographic difference between 2 groups of LN patients. Tregs were significantly lower in active LN compared to inactive LN and healthy control (0.44±0.37% vs. 1.89±0.46% vs. 3.12±0.56% of the CD4+, P<0.001). C3 and C4 complement fragments were significantly reduced in patients with active disease (C3; 50.92±28.43 vs. 76.31±25.63, P=0.011) and (C4; 11.17±8.41 vs. 16.70±6.50 P=0.044). Proteinuria was significantly higher while serum albumin levels were significantly lower in active patients compared to inactive patients and healthy control (urine PCI; 0.25(0.15-0.3) vs. 0.03(0.01-0.05) vs. 0.01, P<0.001) and (albumin; 29.89±6.87 vs. 36.87±3.58 vs. 40.62±1.89mmol/L, P<0.001). We found positive inversely correlation between Tregs with SLEDAI2K (r = -0.572, P=0.011) and proteinuria (r = -0.451, P=0.007).Conclusions: Tregs, C3 and C4 complements, and albumin were significantly lower while proteinuria was significantly higher in active LN. There was positive inversely correlation between the percentage of Tregs with SLEDAI2K score and proteinuria.
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Objective To investigate the effect of Toxoplasma gondii excretory-secretory antigens (ESA) on CD4+ CD25+ Foxp3+ T (Treg) cells in mice carrying Lewis lung carcinoma, and examine the inhibitory effect of T. gondii ESA on tumor growth. Methods C57BL/6 mice were randomly assigned into the PBS group (n = 14) and the Lewis group (n = 34). Mice in the Lewis group were subcutaneously injected with 2 × 105 Lewis lung carcinoma cells in the right axilla, while animals in the PBS group were injected with the same volume of sterile PBS. On day 7 post-injection (D7), mice in the PBS group were further divided into the PBS2 group and the PBS2 + ESA group, of 7 mice in each group, and mice in the Lewis group were further divided into the Lewis2 group and the Lewis2 + ESA group, of 17 mice in each group. Then, mice in the PBS2 + ESA group and the Lewis2 + ESA group were intraperitoneally injected with 100 μL of ESA. The mouse spleen coefficient was calculated in each group 7 days post-injection with ESA, and the changes of Treg cell counts and the long-term tumor growth were measured in tumor-bearing mice. Results The spleen coefficient was significantly greater in the PBS2 + ESA group and the Lewis2 + ESA group than in the PBS2 (0.66% ± 0.09% vs. 0.30% ± 0.02%, P < 0.05) and Lewis2 groups (0.69% ± 0.07% vs. 0.33% ± 0.03%, P < 0.05) 7 days post-treatment with ESA, respectively, and the percentage of splenic Treg cells in splenocytes was significantly lower in the PBS2 + ESA group and the Lewis2 + ESA group than in the PBS2 (1.28% ± 0.14% vs. 2.06% ± 0.07%, P < 0.05) and Lewis2 groups (1.58% ± 0.14% vs. 2.44% ± 0.23%, P < 0.05), respectively. T. gondii ESA treatment caused a delay in tumor growth, and the tumor size was significantly smaller in the Lewis2 + ESA group than in the Lewis2 group (P < 0.05). Conclusion T. gondii ESA may reduce the proportion of splenic Treg cells in splenocytes and inhibit tumor growth in mice carrying Lewis lung carcinoma.
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Objective To investigate the effect of Toxoplasma gondii excretory-secretory antigens (ESA) on CD4+ CD25+ Foxp3+ T (Treg) cells in mice carrying Lewis lung carcinoma, and examine the inhibitory effect of T. gondii ESA on tumor growth. Methods C57BL/6 mice were randomly assigned into the PBS group (n = 14) and the Lewis group (n = 34). Mice in the Lewis group were subcutaneously injected with 2 × 105 Lewis lung carcinoma cells in the right axilla, while animals in the PBS group were injected with the same volume of sterile PBS. On day 7 post-injection (D7), mice in the PBS group were further divided into the PBS2 group and the PBS2 + ESA group, of 7 mice in each group, and mice in the Lewis group were further divided into the Lewis2 group and the Lewis2 + ESA group, of 17 mice in each group. Then, mice in the PBS2 + ESA group and the Lewis2 + ESA group were intraperitoneally injected with 100 μL of ESA. The mouse spleen coefficient was calculated in each group 7 days post-injection with ESA, and the changes of Treg cell counts and the long-term tumor growth were measured in tumor-bearing mice. Results The spleen coefficient was significantly greater in the PBS2 + ESA group and the Lewis2 + ESA group than in the PBS2 (0.66% ± 0.09% vs. 0.30% ± 0.02%, P < 0.05) and Lewis2 groups (0.69% ± 0.07% vs. 0.33% ± 0.03%, P < 0.05) 7 days post-treatment with ESA, respectively, and the percentage of splenic Treg cells in splenocytes was significantly lower in the PBS2 + ESA group and the Lewis2 + ESA group than in the PBS2 (1.28% ± 0.14% vs. 2.06% ± 0.07%, P < 0.05) and Lewis2 groups (1.58% ± 0.14% vs. 2.44% ± 0.23%, P < 0.05), respectively. T. gondii ESA treatment caused a delay in tumor growth, and the tumor size was significantly smaller in the Lewis2 + ESA group than in the Lewis2 group (P < 0.05). Conclusion T. gondii ESA may reduce the proportion of splenic Treg cells in splenocytes and inhibit tumor growth in mice carrying Lewis lung carcinoma.
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Regulatory T (Treg) cells is an indispensable subset of T lymphocyte with the ability of immunosuppression in the periphery.Thymus-derived Treg cells(CD4+CD25+FOXP3+Treg cells) play a fundamental role in maintaining immune homeostasis in vivo.Treg cells have been actively involved in the onset and development of major human diseases including malignant tumors, autoimmune diseases,infectious diseases,allergic diseases and graft versus host disease(GVHD).Exosomes are membranous vesicles of endosomal origin that released from multiple cells into the extracellular space.They are currently considered to be vehicles containing protein,RNA and MicroRNA which can been transferred to recipient cells to modulate their activity by cell-contact-independent mecha-nism.Exosomes have a great impact on the induction and proliferation of Treg cells,understanding the relation of them will lead to novel therapeutic approaches for cancer immunotherapy,treating autoimmunity,infection,allergy and organ transplantation.
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Objective To compare the synchronous changes of high risk human papillomavirus load(HPV-DNA)and CD4+CD25+Foxp3+regulatory T cells(Treg)in local microenvironment of cervix,and investigate the ef-fects of HPV virus replication and progression of cervical lesions on Treg cells. Methods 304 cases of HR-HPV infection with cervical lesions were divided into 5 groups,cervical intraepithelial neoplasia(CIN)I,CINII,CINIII, cervical cancer and chronic cervicitis.The HPV-DNA of cervical secretion was detected by PCR fluorescence,and the relative Treg cells numbers from cervical brush samples were determined by flow cytometry with CD4+CD25+Foxp3+gating,and the data were statistically analyzed. Results(1)There was significant difference of cervical Treg cells in different degrees of cervical lesion and different copy numbers by variance comparison(F = 24.93, 109.86,P < 0.05),and a further pairwise comparison showed that there was no significant difference of Treg cell between chronic cervicitis and CINI and low load(HPV DNA 104~105copies/mL)and medium load(HPV DNA 105~106copies/mL)(P>0.05).There was a significant difference between the other groups(P<0.05);(2)Treg cells as variable,interaction effect of cervical lesions and viral load factors were significant different(F=3.39,P<0.05). The effect of different cervical lesions and HR-HPV viral load on the expression of Treg cells was differen-tial. An overall showing with the degree of cervical lesions increased,HR-HPV virus copy number increased, Treg cells expression increased gradually;(3)CD4+CD25+Foxp3+Treg cells were highly expressed in cervical cancer patients,but the expression level fluctuated widely and the numerical distribution was the most dispersedly. Conclusion The immune suppression function of local CD4+CD25+Foxp3+Treg cells with different cervical lesions and different HR-HPV DNA may bilaterally regulate the prognosis of cervical lesions,as a whole,between Treg cells and HR-HPV load and cervical lesions were the consistent progress trend.
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<p><b>Background </b>: Shigyakusan, a 4-component Japanese herbal medicine (Paeoniae radix, Aurantii fructus immaturus, Glycyrrhizae radix and Bupleuri radix), is used not only for cholecystitis and gastritis as an antiinflammatory agent, but also for anxiety neurosis and insomnia as an anti-anxiety agent.<br><b>Methods </b>: We investigated the effects of shigyakusan on alloimmune responses in fully MHC-mismatched murine cardiac allograft transplantation. CBA mice underwent transplantation of a C57BL/6 heart and received shigyakusan or one component of shigyakusan administered orally from the day of transplantation until 7 days afterward. Histologic studies, cytokine measurements, and flow cytometry assessments were performed.<br><b>Results </b>: Untreated CBA recipients acutely rejected C57BL/6 cardiac grafts (median survival times [MST], 7 days). On the other hand, CBA transplant recipients given shigyakusan had significantly prolonged C57BL/6 allograft survival (MST, 22.5 days). MSTs for C57BL/6 transplant recipients given Paeoniae radix, Aurantii fructus immaturus, Glycyrrhizae radix and Bupleuri radix were 11, 9.5, 18.5 and 8 days, respectively. Additionally, flow cytometry studies showed that the percentage of CD25+Foxp3+ cell populations in CD4+ cells was increased in transplant recipients given shigyakusan.<br><b>Conclusion </b>: Shigyakusan induced hyporesponsiveness to fully MHC-mismatched allogeneic cardiac allografts and may generate CD4+CD25+Foxp3+ cells in our model.</p>
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Objective To explore the relationship between HBeAg in HBsAg positive mothers and CD4 + CD25 + Foxp3 + regulatory T cells (Treg) in newborns,as well as how they would influence the increasing risk on HBV intrauterine transmission.Methods We collected information on general demographic characteristics and delivery on 270 HBsAg positive mothers and their newborns from the Third People's Hospital of Taiyuan.Fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA) were used to detect HBV DNA and HBV serological markers in peripheral blood from both mothers and neonates.The expression of Treg and other immune cells in peripheral blood of neonates were detected with flow cytometry (FCM).Results Maternal HBeAg positive rates were associated with an increased risk of intrauterine transmission (0R=4.08,95％ CI:1.89-8.82).Rates of T.reg in newborns born to HBsAg-positive mothers were higher than that of the negative group (Z=2.29,P=0.022).Each pair of the subjects was assigned to five different groups according to the HBeAg titers of mothers.Frequencies of both Treg and HBeAg in newboms and HBV DNA in mothers between the above said 5 groups showed similar trends of changing patterns and the differences between groups were statistically significant (x2=18.73,P＜0.001;x2=181.60,P＜0.001;x2=183.09,P＜0.001).Results from partial correlation analysis showed that after adjusting for neonatal HBeAg and maternal HBV DNA,mother's HBeAg titers were positively related to the percentage of Treg in their newboms (rs=0.19,P=0.039).In addition,the frequencies of Treg were negatively correlated with pDC and CD4 + T cell in their newborns (rs=-0.21,P=0.017;r,=-0.23,P=0.009).Conclusion HBeAg from HBsAg positive mothers might have inhibited the function of neonatal DC cells and T cells to reduce the immune response to HBV by up-regulating the proportion of Treg and finally increased the risk of HBV intrauterine transmission.
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Objective To explore the relationship between HBeAg in HBsAg positive mothers and CD4 + CD25 + Foxp3 + regulatory T cells (Treg) in newborns,as well as how they would influence the increasing risk on HBV intrauterine transmission.Methods We collected information on general demographic characteristics and delivery on 270 HBsAg positive mothers and their newborns from the Third People's Hospital of Taiyuan.Fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA) were used to detect HBV DNA and HBV serological markers in peripheral blood from both mothers and neonates.The expression of Treg and other immune cells in peripheral blood of neonates were detected with flow cytometry (FCM).Results Maternal HBeAg positive rates were associated with an increased risk of intrauterine transmission (0R=4.08,95％ CI:1.89-8.82).Rates of T.reg in newborns born to HBsAg-positive mothers were higher than that of the negative group (Z=2.29,P=0.022).Each pair of the subjects was assigned to five different groups according to the HBeAg titers of mothers.Frequencies of both Treg and HBeAg in newboms and HBV DNA in mothers between the above said 5 groups showed similar trends of changing patterns and the differences between groups were statistically significant (x2=18.73,P＜0.001;x2=181.60,P＜0.001;x2=183.09,P＜0.001).Results from partial correlation analysis showed that after adjusting for neonatal HBeAg and maternal HBV DNA,mother's HBeAg titers were positively related to the percentage of Treg in their newboms (rs=0.19,P=0.039).In addition,the frequencies of Treg were negatively correlated with pDC and CD4 + T cell in their newborns (rs=-0.21,P=0.017;r,=-0.23,P=0.009).Conclusion HBeAg from HBsAg positive mothers might have inhibited the function of neonatal DC cells and T cells to reduce the immune response to HBV by up-regulating the proportion of Treg and finally increased the risk of HBV intrauterine transmission.
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Objective To investigate the expression and significance of Th9, Th17 and CD4+CD25+Foxp3+regulatory T (Treg) cells as well as the related cytokines (IL-9, IL-17, TGF-β) in peripheral blood of patients with adult primary immune thrombocytopenia ( ITP) . Methods Peripheral blood samples were collected from 47 patients with ITP and 39 age-and sex-matched healthy subjects. The percentages of Th9, Th17 and CD4+CD25+Foxp3+Treg cells in peripheral blood samples were detected with flow cytometry. The levels of IL-9, IL-17 and TGF-βin serum samples were detected by enzyme linked immunosorbent assay ( ELISA) . Results Compared with healthy subjects, the percentages of Th9 and Thl7 cells and the concen-trations of IL-9 and IL-17 in patients with ITP were significantly increased [(1. 27±0. 31)% vs (0. 71± 0. 26)%, P<0. 05;(2. 01±0. 42)% vs (0. 97±0. 32)%, P<0. 05. (26. 52±7. 48) ng/L vs (16. 16± 5. 27) ng/L, P<0. 05;(10. 97±3. 94) ng/L vs (7. 14±2. 73) ng/L, P<0. 05]. The percentages of CD4+CD25+Foxp3+ Treg cells and the concentrations of TGF-β in patients with ITP were lower than those in healthy subjects [(4. 69±0. 85)% vs (7. 16±1. 92)%, P<0. 05. (3. 76±1. 28) μg/L vs (6. 41±1. 83)μg/L, P<0. 05]. Moreover, the blood platelet counts in patients with ITP were negatively correlated with the percentages of Th9 and Th17 cells and the concentrations of IL-9 and IL-17 (γs=-0. 349, P=0. 037;γs=-0. 392, P=0. 031;γs=-0. 436, P=0. 014;γs=-0. 401, P=0. 027), but were positively correlated with the percentages of CD4+CD25+Foxp3+ Treg cells and the concentrations of TGF-β (γs=0. 411, P=0. 024;γs=0. 407, P=0. 026). Conclusion The imbalanced distribution of Th9, Th17 and Treg cells and the abnormal expression of related cytokines (IL-9, IL-17 and TGF-β) in patients with ITP might be the possible immunological pathogenesis of ITP.
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The mechanism underlying CD4CD25Foxp3regulatory T cells (Tregs) promoting the development of colorectal cancer (CRC) was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4CD25Foxp3Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues (P< 0.01). Pearson correlation analysis indicated that the expression level of Foxp3 was positively correlated with Stat3 at mRNA level (r=0.526, P=0.036), and was positively correlated with IL-10 at protein level (r=0.314, P=0.030). The Foxp3 expressed in CD4CD25Foxp3Tregs was correlated with the histological grade, lymph node metastasis and TNM stage of CRC (P<0.05 for all). The IL-10 expression was correlated with the histological grade and TNM stage (both P<0.05). The Stat3 expression was correlated with the lymph node metastasis and TNM stage (both P<0.05). It was concluded that CD4CD25Foxp3Tregs can inhibit tumor immunity in combination with some other related inhibitory cytokines and that Foxp3 expression in CD4CD25Foxp3Tregs correlates with CRC progression.
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Adult , Aged , Female , Humans , Male , Middle Aged , CD4-Positive T-Lymphocytes , Allergy and Immunology , Colorectal Neoplasms , Genetics , Allergy and Immunology , Pathology , Forkhead Transcription Factors , Genetics , Allergy and Immunology , Gene Expression Regulation, Neoplastic , Allergy and Immunology , Immunity , Genetics , Interleukin-10 , Allergy and Immunology , Interleukin-2 Receptor alpha Subunit , Allergy and Immunology , Lymphatic Metastasis , STAT3 Transcription Factor , Allergy and Immunology , T-Lymphocytes, Regulatory , Allergy and ImmunologyABSTRACT
As most infections by the helminth parasite elicit the recruitment of CD4+CD25+Foxp3+ T (T(reg)) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated T(reg) cells, we compared the expression levels of T(reg) cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of T(reg) cells was monitored using GFP-coded Foxp3 transgenic mice. In mice at 1 week after Trichinella spiralis infection, the number of activated T(reg) cells was higher than in the control group. In mice at 2 weeks after infection, there was a significant increase in the number of cells expressing Foxp3 and CTLA-4 when compared to the control group and mice at 1 week after infection. At 4 weeks after infection, T. spiralis was easily identifiable in nurse cells in mouse muscles. In the intestine, the expression of Gzmb and Klrg1 decreased over time and that of Capg remained unchanged for the first and second week, then decreased in the 4th week. However, in the muscles, the expression of most chemokine genes was increased due to T. spiralis infection, in particular the expression levels of Gzmb, OX40, and CTLA-4 increased until week 4. In addition, increased gene expression of all chemokine receptors in muscle, CXCR3, CCR4, CCR5, CCR9, and CCR10, was observed up until the 4th week. In conclusion, various chemokine receptors showed increased expressions combined with recruitment of T(reg) cells in the muscle tissue.
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Animals , Mice , Gene Expression , Helminths , Ileum , Inflammation , Intestines , Mice, Transgenic , Muscles , Parasites , Receptors, Chemokine , T-Lymphocytes, Regulatory , Trichinella spiralis , TrichinellaABSTRACT
Objective To observe the expression level of CD4+ CD25+ Foxp3+ regulatory T cells in the peripheral blood of acute and stable senile COPD patients ,and analyze the correlation between Treg cells and TGF‐β1 of senile COPD ,then investigate the role of Treg cells and TGF‐β1 in the onset of senile COPD .Methods Totally 26 patients with acute stage and 23 patients with stable stage were investigated as acute group and stable group ,they came from the department of geriatric of our hospital form March ,2012 to February ,2014 .Meanwhile ,20 healthy people were selected as control group .The proportion of Treg cells in pe‐ripheral blood was measured by flow cytometry method and the level of TGF‐β1 in serum was measured by ELISA .Results The percentage of Treg on peripheral blood in acute and stable groups were significantly higher than control group(P0 .05) .Conclusion Treg cells may be involved in the process of the pathogenesis of senile COPD and acute exacerbation .There is no correlation between the proportion of Treg cells and TGF‐β1 ,and it indicates immune disorders may exist in senile COPD patients .
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Objective To explore the effect of Lactobacillussalivariuson the number of CD4+CD25+Foxp3+Treg cells and expression of transform?ing growth factorβ1(TGF?β1)in asthma Balb/c mice. Methods Thirty?two female Balb/c mice were randomly divided into four groups:the nor?mal control group,the asthma group,the Lactobacillus salivarius group,and the asthma combined Lactobacillussalivariusgroup. Acute asthma mod?el was established by the ovalbumin challenge method. After extraction of primary spleen cells,flow cytometry was used to test CD4+CD25+Foxp3+Treg/CD4+T ratio in spleen lymphocytes. The levels of IL?4,IFN?γand TGF?β1 in the spleen cell culture supernatant were measured by ELISA method. Results The level of Th2 cytokine(IL?4)in the spleen cell culture supernatant of the asthma group was significantly higher than that of the control group(P<0.05),however,the level of Th1 cytokine(IFN?γ)was significantly lower than that of the control group(P<0.05). The ex?pression level of Th2 cytokine(IL?4)in the Lactobacillussalivariusintervention group was significantly decreased compared with the asthma group, and the Th1 cytokine(IFN?γ)expression level was elevated compared with the asthma group(P<0.05). The level of TGF?β1 in the Lactobacillus salivarius intervention group was higher than in the asthma group(P<0.05). The proportion of CD4+CD25+Foxp3+Treg/CD4+T in spleen lympho?cytes in the asthma group was lower than that in the control group(P<0.05),and was higher in the Lactobacillus salivarius intervention group than in the asthma group(P<0.05). Conclusion CD4+CD25+Foxp3+Treg was associated with the pathogenesis of asthma. Lactobacillus salivarius could adjust Th1/Th2 imbalance and reduce asthma inflammation through up?regulation of CD4+CD25+Foxp3+Treg and TGF?β1 expression.
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Objective:To investigate the effect of the adoptive transfer of CD4+CD25+Foxp3+regulatory T cells ( iTregs) induced by 5-aza-2′-deoxycytidine (5AzaD) on pregnant outcome of the abortion-prone mice.Methods:Sixty cases of female CBA/J × male DBA/2J abortion-prone matings were taken as study group,the CD4+T cells from spleen of twenty female CBA/J mice were separated by magnetic activated cell sorting (MACS),5AzaD was applied to the conversion of CD4+CD25-T cells to iTregs,the expression of Foxp3 in Tregs was characterized by flow cytometry analysis before and after epigenetic modification.The purified iTregs were injected into abortion-prone mice on day 1 or 4 of pregnancy,respectively,which were used as therapy groups,and then the embryo resorption rate was counted on day 14 of pregnancy.Results:After the treatment of 5AzaD,the percentage of iTregs in CD4+T cells was (41.50±8.03)%.The embryonic absorption rates of the two therapy groups were 10.47%(on day 1 of pregnancy) and 21.69%(on day 4 of pregnancy) ,respectively ( P<0.05 ) .Conclusion: Epigenetic modication of CD4+CD25-T cells may solve the problem of nTregs deficiency,particularly adoptive therapy of 5AzaD-induced iTregs at early stage of pregnancy can maintain normal pregnancy.
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BACKGROUND: Regulatory T cells (Treg) are able to inhibit the immunological response and maintain cutaneous immunological homeostasis, thus preventing autoimmunity against itself. In several studies, the importance of CD4+CD25+Foxp3+ Treg in psoriasis has been examined, using the peripheral blood of patients. However, limited studies on Treg are available and shows conflicting results. Recently, CD4+CD25-Foxp3+ T cells were identified as being the peripheral reservoir of CD4+CD25+Foxp3+ Treg. OBJECTIVE: The purpose of this study was to investigate differences in the CD4+CD25+Foxp3+ Treg and CD4+CD25- Foxp3+ T cell counts between patients with psoriasis and normal controls. METHODS: For phenotypic analysis, the proportions and absolute cell numbers of CD4+CD25+Foxp3+ Treg and CD4+CD25-Foxp3+ T cells in the peripheral blood were examined by flow cytometry. The correlation between the CD4+CD25+Foxp3+ Treg count and other parameters (age of onset, disease duration, BSA, psoriasis area and severity index score, and clinical stage) was also analyzed. RESULTS: Although the CD4+CD25+Foxp3+ Treg count was slightly increased while the number of CD4+CD25- Foxp3+ T cells was slightly decreased in psoriasis patients than that of the controls, the differences between the groups were not statistically significant (5.27+/-2.60 vs. 4.70+/-1.35, p>0.05; 1.56+/-1.07 vs. 1.93+/-1.08, p>0.05). The CD4+CD25+Foxp3+ Treg count did not correlate with the tested parameters except for the clinical stage of psoriasis. The mean+/-SD number of CD4+CD25+Foxp3+ Treg in the stable phase was higher than that in the progressive phase (7.26+/-2.58 vs. 4.35+/-2.10, p0.05). CONCLUSION: These findings suggest that the CD4+CD25+Foxp3+ Treg count alone is insufficient to explain the pathogenesis and severity of psoriasis. However, a decrease in circulating CD4+CD25+Foxp3+ Treg is likely to be correlated with an aggravation of psoriasis.
Subject(s)
Humans , Autoimmunity , Cell Count , Flow Cytometry , Homeostasis , Psoriasis , T-Lymphocytes , T-Lymphocytes, RegulatoryABSTRACT
BACKGROUND: Regulatory T cells (Treg) are able to inhibit the immunological response and maintain cutaneous immunological homeostasis, thus preventing autoimmunity against itself. In several studies, the importance of CD4+CD25+Foxp3+ Treg in psoriasis has been examined, using the peripheral blood of patients. However, limited studies on Treg are available and shows conflicting results. Recently, CD4+CD25-Foxp3+ T cells were identified as being the peripheral reservoir of CD4+CD25+Foxp3+ Treg. OBJECTIVE: The purpose of this study was to investigate differences in the CD4+CD25+Foxp3+ Treg and CD4+CD25- Foxp3+ T cell counts between patients with psoriasis and normal controls. METHODS: For phenotypic analysis, the proportions and absolute cell numbers of CD4+CD25+Foxp3+ Treg and CD4+CD25-Foxp3+ T cells in the peripheral blood were examined by flow cytometry. The correlation between the CD4+CD25+Foxp3+ Treg count and other parameters (age of onset, disease duration, BSA, psoriasis area and severity index score, and clinical stage) was also analyzed. RESULTS: Although the CD4+CD25+Foxp3+ Treg count was slightly increased while the number of CD4+CD25- Foxp3+ T cells was slightly decreased in psoriasis patients than that of the controls, the differences between the groups were not statistically significant (5.27+/-2.60 vs. 4.70+/-1.35, p>0.05; 1.56+/-1.07 vs. 1.93+/-1.08, p>0.05). The CD4+CD25+Foxp3+ Treg count did not correlate with the tested parameters except for the clinical stage of psoriasis. The mean+/-SD number of CD4+CD25+Foxp3+ Treg in the stable phase was higher than that in the progressive phase (7.26+/-2.58 vs. 4.35+/-2.10, p0.05). CONCLUSION: These findings suggest that the CD4+CD25+Foxp3+ Treg count alone is insufficient to explain the pathogenesis and severity of psoriasis. However, a decrease in circulating CD4+CD25+Foxp3+ Treg is likely to be correlated with an aggravation of psoriasis.
Subject(s)
Humans , Autoimmunity , Cell Count , Flow Cytometry , Homeostasis , Psoriasis , T-Lymphocytes , T-Lymphocytes, RegulatoryABSTRACT
Objective To investigate the regulatory effects of IFN-γon Treg cells from HIV/AIDS patients receiving highly active antiretroviral therapy (HAART) for one year.Methods Thirty HIV/A1DS patients whose CD4+T cells were below 350/μ1 were recruited for HAART therapy.Blood samples were collected at the time points of 0,24,48 weeks after HAART.PBMCs were isolated and randomly divided into two culture groups.One group was cultured directly in medium and another group was co-cultured with IFN-γ (40 pg/ml).The supernatants and cells were separated after 5 days of culture for analysis.The concentrations of IL-12 and CD4+CD25+Foxp3 Treg cells were measured by ELISA and flow cytometry,respectively.Results The levels of IL-12 in the supernatants from the culture without IFN-γ at time points of 0,24,48 weeks after HAART were lower than those from the co-cultured group [(37.02±12.76) vs (41.79± 15.02),t=2.336,P=0.03; (41.76±17.01) vs (47.2±14.26),t=2.702,P=0.014; (48.01± 11.84) vs (53.44± 11.30),t =3.14,P =0.003].The percentages of CD4+ CD25 + Foxp3 Treg cells in CD4+ T cells from the direct-cultured group were higher than those from the co-cultured group at the three time points [(10.41±1.10)％ vs (2.40±1.11)％,t=13.89,P=0.000; (8.33±2.03)％ vs (1.99± 0.86)％,t=12.93,P=0.000; (5.65±1.55)％ vs (1.32±0.73)％,t=10.61,P=0.000].Moreover,the results within the same group at the time points of 0,24,48 weeks upon HAART were also significantly different.Conclusion With the interference of HAART,IL-12 levels were increased,while CD4+CD25+ Foxp3 Treg cells were decreased in patients with HIV/AIDS.IFN-γ plays an important role in this process.
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Scholars at home and abroad have proved that the unbalance between CD4 + CD25 + Foxp3 +regulatory T cells (Treg cells) and Th17 cells relates to the pathogenesis of hematopathy.Patients with tumor blood diseases,such as leukemia and lymphoma,generally show raised levels of Treg cells and decreased levels of Th17 cells.The pathogenesis of disease may involve in Treg cells inducing enhanced immune suppression and Th17 cells mediating immune deficiency.On the contrary,cases with non-neoplastic blood diseases,such as AA,HSP,ITP and so on,trend to have lower Treg cells and higher Th17 cells.The pathogenesis of non-neoplastic blood disease may be connected with serious immune injury mediated by Th17 cells and weak suppression of immunity induced by Treg cells.Accordingly,the increasing ratio of Treg cells/Th17 cells may cause tumor blood diseases,but a decreasing one can promote non-neoplastic blood disease.
ABSTRACT
Different functions have been attributed to CD4+CD25+Foxp3+ regulatory T-cells (Tregs) during malaria infection. Herein, we describe the disparity in Treg response and pro- and anti-inflammatory cytokines during infection with Plasmodium berghei ANKA between young (3-week-old) and middle-aged (8-month-old) C57BL/6 mice. Young mice were susceptible to cerebral malaria (CM), while the middle-aged mice were resistant to CM and succumbed to hyperparasitemia and severe anemia. The levels of pro-inflammatory cytokines, such as TNF-alpha, in young CM-susceptible mice were markedly higher than in middle-aged CM-resistant mice. An increased absolute number of Tregs 3-5 days post-inoculation, co-occurring with elevated IL-10 levels, was observed in middle-aged CM-resistant mice but not in young CM-susceptible mice. Our findings suggest that Treg proliferation might be associated with the suppression of excessive pro-inflammatory Th1 response during early malaria infection, leading to resistance to CM in the middle-aged mice, possibly in an IL-10-dependent manner.
Subject(s)
Animals , Female , Mice , Aging/immunology , Cytokines/genetics , Gene Expression Regulation , Malaria/immunology , Plasmodium berghei/classification , T-Lymphocytes, Regulatory/classificationABSTRACT
Objective To observe the changes of number and proportion of CD4+CD25+FOXP3+ cells in peripheral blood of active rheumatoid arthritis patients (RA),and explore the function of recombinant human TNFR Ⅱ-Fc on the CD4+CD25-FOXP3+ Treg cells.Methods ① Forty severe RA patients were selected,who were divided into the combined treatment group (TNFR Ⅱ-Fc+MTX) and MTX only group according to the principle of randomized,double-blind,parallel and placebo-controlled study.All patients were treated for 12 weeks.Flow cytometry was used to analyze and compare the expression ratio of CD4+CD25+FOXP3 +Treg cells of RA patients' peripheral blood.Forty healthy controls were selected for parallel comparison.② VAS,DAS28,HAQ average of the two groups at different periods were compared.Matched t test was used to examine the quantity data between the groups.Results ① The proportion of CD4+CD25+FOXP3+ cells in the peripheral blood of active rheumatoid arthritis patients was significantly lower than healthy group [ (5.4±1.4)％ vs ( 7.5±1.5 )％,P＜0.01 ].The proportion of CD4+CD25+ FOXP3+ Treg cells in combined treatment group was significantly higher [(7.0+1.2)％ vs (5.2±1.6)％,P＜0.01 ] after TNFR Ⅱ-Fc and MTX combination therapy for 12 weeks.The increase rate of CD4+CD25+FOXP3+Treg cells in combined treatment group was evidently more remarkable than MTX only group [ (7.0 ± 1.2)％ vs (5.6 ±0.7 )％,P＜0.01].② After 12 weeks treatment,the arerage scores of VAS,DAS28 and HAQ of the combined treatment group were better than MTX only group,and the difference was statistically significant (P＜0.01).Conclusion This study has shown that the healing effect of TNFR Ⅱ -Fc combined with MTX is better than MTX only.TNFR Ⅱ -Fc can restore and improve the proportion of CD4+CD25+FOXP3+ Treg cells in active RA patients,which is likely to be an important mechanism for the treatment of RA patients.