Bacterial dissemination in Mycobacterium tuberculosis by CD+ T-cells & proinflammatory cytokines

Background & objectives: As CD4+ and CD8+ T lymphocyte numbers decline, the conventional, localized forms of tuberculosis shift to the atypical, disseminated forms. Variations in lymphocyte and immune cell expression levels affect how tuberculosis manifests in disseminated forms. Understanding the relationship between lymphocyte counts (CD4+ and CD8+) and pro-inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-12 and interferon, we may therefore be able to shed light on how infections spread and suggest potential biomarkers for these immune factors. Methods: In this study, 15 guinea pigs were infected with Mycobacterium tuberculosis (M.tb) H37Rv strain and grouped into three groups of five each for further investigation. Serum samples and bronchoalveolar lavage (BAL) fluid were examined for the expression of pro-inflammatory cytokines and T-cell subsets in guinea pigs infected with pulmonary tuberculosis and disseminated tuberculosis. Results: We found that M.tb escapes macrophages due to pro-inflammatory cytokine dysregulation. Despite the protective immunity created by T-cells and cytokines, M.tb bacilli may spread to other organs due to inflammation induced by these immune components. A high number of T-cells and stimulated cytokine production are involved in triggering inflammation after necrotic tissue develops and tuberculosis spreads. Interpretation & conclusions: Our findings imply that increased bacilli in the spleen at the 8th wk of infection may be caused by the overexpression of CD4+ T-cell lymphocyte subsets and cytokines that generated inflammation during the 4th wk of infection. This is a pilot study with a small sample size and less assertive inference. Larger studies would be helpful to validate the results of the present investigation.

A bioinformatic analysis of the role of TP53 status on the infiltration of CD8+ T cells into the tumor microenvironment

CD8+ T cells play basic roles in the immune system in a tumor microenvironment (TME) to fight cancer. Several reports have suggested signs of the involvement of tumor protein p53 (TP53) in a complex immune system network. Moreover, our previous research indicated that TP53 orchestrates the polarization and infiltration of macrophages into the TME. In the present study, the clinical function of TP53 status (wild/mutant) in CD8+ T cell infiltration was assessed using more than 10,000 The Cancer Genome Atlas (TCGA) samples from 30 cancer types through Tumor Immune Estimation (TIMER). Our investigation revealed that CD8+ T cell infiltration was higher in head and neck squamous cell carcinoma (HNSC) and uterine corpus endometrial carcinoma (UCEC) patients with wild-type TP53 than in those with mutant TP53. Wild-type TP53 conferred a good prognosis for HNSC and UCEC (P<0.05). In contrast, CD8+ T cell infiltration in lung adenocarcinoma (LUAD) patients with wild-type TP53 was much lower than in those with mutant TP53. Notably, clinical outcomes for LUAD with wild-type TP53 were poor (P<0.05). This study was the first to provide insights into the novel association of TP53 with CD8+ T cells infiltration in the TME in patients with HNSC, LUAD, and UCEC. Therefore, TP53 status acts as a prognostic marker, and this can be used as a basis to further study the effect of targeting TP53 in these patients. Furthermore, our study found that TP53 status was a reliable predictive factor and therapeutic target in patients with HNSC and UCEC.

Sialic acid-mediated photochemotherapy enhances infiltration of CD8+ T cells from tumor-draining lymph nodes into tumors of immunosenescent mice

Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8+ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8+ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8+ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.

Chang Wei Qing Decoction enhances the anti-tumor effect of PD-1 inhibitor therapy by regulating the immune microenvironment and gut microbiota in colorectal cancer / 中国天然药物

The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment (TIME). This study aimed to mechanistically assess whether Chang Wei Qing (CWQ) Decoction can enhance the anti-tumor effect of PD-1 inhibitor therapy. PD-1 inhibitor therapy showed the significant anti-tumor effect in patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC), rather than those with mismatch repair-proficient/microsatellite stable (pMMR/MSS) CRC. Hence, immunofluorescence double-label staining was utilized to explore the difference in the TIME between dMMR/MSI-H and pMMR/MSS CRC patients. Flow cytometry was used to analyze T-lymphocytes in tumors from mice. Western blot was used to measure the expression of PD-L1 protein in mouse tumors. The intestinal mucosal barrier of mice was evaluated by hematoxylin-eosin staining and immunohistochemistry. 16S rRNA-gene sequencing was used to examine the structure of the gut microbiota in mice. Subsequently, Spearmanapos;s correlation analysis was used to analyze the relationship between the gut microbiota and tumor-infiltrating T-lymphocytes. The results showed that dMMR/MSI-H CRC patients had more CD8+T cells and higher expression of PD-1 and PD-L1 proteins. In vivo, CWQ enhanced the anti-tumor effect of anti-PD-1 antibody and increased the infiltration of CD8+ and PD-1+CD8+ T cells in tumors. Additionally, the combination of CWQ with anti-PD-1 antibody resulted in lower inflammation in the intestinal mucosa than that induced by anti-PD-1 antibody alone. CWQ and anti-PD-1 antibody co-treatment upregulated PD-L1 protein and reduced the abundance of Bacteroides in the gut microbiota but increased the abundance of Akkermansia,Firmicutes, andActinobacteria. Additionally, the proportion of infiltrated CD8+PD-1+, CD8+, and CD3+ T cells were found to be positively correlated with the abundance of Akkermansia. Accordingly, CWQ may modulate the TIME by modifying the gut microbiota and consequently enhance the anti-tumor effect of PD-1 inhibitor therapy.

Expression of TIGIT, PD-1 and HLA-DR/CD38 markers on CD8-T cells of children and adolescents infected with HIV and uninfected controls

ABSTRACT Immune exhaustion and senescence are scarcely studied in HIV-pediatric patients. We studied the circulatory CD8 T cells activation/exhaustion and senescent phenotype of children and adolescents vertically infected with HIV or uninfected controls based on the expression of human leukocyte antigen (HLA-DR), CD38, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), programmed death 1 (PD-1) and CD57 by flow cytometry, during approximately one year. Eleven HIV-infected (HI) and nine HIV-uninfected (HU) children/adolescents who received two doses or one dose of meningococcal C conjugate vaccine (MenC), respectively, were involved in this study. Blood samples were collected before the immunization (T0), 1-2 months after the first dose (T1), and 1-2 months after the second dose (T2), which was administered approximately one year after the first one. HI patients not receiving combined antiretroviral therapy (cART) showed a higher frequency of CD8 T cells TIGIT+, PD-1+ or CD57+, as well as a higher frequency of CD8 T cells co-expressing CD38/HLA-DR/TIGIT or CD38/HLA-DR/PD-1 when compared to HI treated or HU individuals, at all times that they were assessed. CD8 T cells co-expressing CD38/DR/TIGIT were inversely correlated with the CD4/CD8 ratio but positively associated with viral load. The co-expression of CD38/DR/TIGIT or CD38/DR/PD-1 on CD8 T cells was also inversely associated with the CD4 T cells expressing co-stimulatory molecules CD127/CD28. The results showed a higher expression of exhaustion/senescence markers on CD8 T cells of untreated HI children/adolescents and its correlations with viral load.

Increased tumor-associated mast cells facilitate thyroid cancer progression by inhibiting CD8+ T cell function through galectin-9

As an important component of solid tumors, mast cells show specific phenotypes in various tumor microenvironments. However, the precise mechanism of mast cell accumulation and the phenotypic features of thyroid cancer (TC) remain largely unknown. Here, we found that mast cells were obviously recruited to tumor tissue by TC-derived stem cell factor (SCF). With tumor progression, mast cell levels increased gradually. In addition, intratumoral mast cells expressed higher levels of the immunosuppressive molecule galectin-9, which effectively suppresses CD8+ T-cell antitumor immunity in vitro. Blocking galectin-9 on tumor-infiltrating mast cells reversed the immunosuppression of CD8+ T cells. In conclusion, our data elucidated novel protumorigenic and immunosuppressive roles of mast cells in TC. In addition, our results indicated that blocking mast cells may impede tumor progression and ameliorate the prognosis of TC patients.

Potentiating CD8

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8

Pathogenesis of CD8+ T cells in dextran sulfate sodium-induced murine acute colitis / 上海交通大学学报（医学版）

Objective: To investigate the role of CD8+ T cells in the pathogenesis of acute murine colitis induced by dextran sulfate sodium (DSS). Methods: Wild type and CD8 knock-out (CD8-/-) mice with C57BL/6 background were given DSS with concentration of 2% (m/V). The body weight, colon length, pathological changes and disease activity of colitis were observed dynamically. The total RNA was extracted from the distal colon of mice after induction for 10 d. The mRNA expression of inflammatory cytokines Il1b, Il6, Il17a, Ifng, Tnf, Il10 and Tgfb1 were detected by real-time quantitative PCR. Colon tissue sections were stained with hematoxylin-eosin (H-E) and the changes of intestinal histopathology were evaluated, and the infiltration of CD8+ T cells in colon tissue was observed by immunofluorescence staining. The survival rate of mice was observed with 3% and 4% (m/V) DSS solution-induced colitis models. Results: After CD8-/- mice being induced by 2% DSS, the body weight decreased slowly and showed an increasing trend on the 9th day, while the pathological changes of colon tissues of CD8-/- mice were slight. The expression levels of Il1b, Il6, Il17a, Ifng and Tnf mRNA were lower than those of wild-type mice (P<0.05). The number of CD8+ T cells in colonic lamina propria of wild-type mice with 2% DSS induction was higher than that of wild-type mice without DSS treatment (P=0.001). The survival rates of wild-type mice induced by 3% and 4% DSS were 37.5% and 0, and the survival rates of CD8-/- mice were 66.7% and 100%, while the survival rates of CD8-/- mice receiving 3% and 4% DSS were higher than those of wild-type mice (P=0.025, P=0.001). Conclusion: CD8+ T cells can promote the development of murine acute DSS-induced colitis.

Expression and clinical significance of B and T lymphocyte attenuator on CD4+ and CD8+ T cells from patients with pulmonary tuberculosis

Background: As an immune checkpoint, upregulation of B and T lymphocyte attenuator (BTLA) contributes to T-cell exhaustion in chronic infection. However, the characteristics of BTLA on T cells of patients with pulmonary tuberculosis (PTB) are still uncovered. Aims: The aim of the study was to elucidate the dynamics and clinical significance of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients. Materials and Methods: BTLA expression on T cells from PTB patients with smear positivity (n = 86) and healthy controls (HCs) (n = 40) were determined using flow cytometry. Results: The levels of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients with smear positivity were both upregulated, compared with HC. At the same time, the levels of BTLA expression on CD4+ and CD8+ T cells of patients with retreatment were both higher than that of those with initial treatment and gradually upregulated along with the increase of the bacillary load in sputum. In addition, the patients with lung cavity were discovered to present higher levels of BTLA expression on CD4+ and CD8+ T cells than those without lung cavity. Whereas we noted that there was no correlation between the levels of BTLA expression and the positivity or negativity of anti-Mycobacterium tuberculosis antibody. Conclusions: The levels of BTLA expression were upregulated on CD4+ and CD8+ T cells of PTB patients and associated with disease progression. Thereby, BTLA expression on T cells may be considered as a potential clinical indicator and utilized as a therapeutic target for PTB.

Innate and adaptive T cells in influenza disease / 医学前沿

Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses (T cells and antibody-producing B cells) achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T-cells (MAIT cells, γδ cells, and NKT cells) in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and γδ T cells as well as adaptive CD8 and CD4 T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.

A potential role of macrophage phenotypes in the early evaluation of the effects of combined Yersinia Pestis and Brucella bovis vaccine immunization / 国际药学研究杂志

Objective In emergency situations where simultaneous immunization by multiple vaccines are required,how to rapidly evaluate the effect of combined immunization is an urgent issue that needs to be solved.This study aimed to investigate the po-tential role and application value of the phenotypic changes of macrophages in rapid evaluation of the effect of combined Yersinia pestis and Brucella bovis vaccine immunization at early stage.Methods Y.pestis and B.bovis vaccines were injected into mice alone or in combination to establish animal models.The changes of the macrophage phenotypes(M1 or M2 polarization)and the CD8+T cell pheno-types and functions were detected in the early(4 d)and the late(14 d)stage of the immunization,respectively.The effect of the immuno-phenotype of macrophages at early stage on the function of CD8+T cells at late stage was analyzed.Results The co-immunization by Y.pestis and B.bovis vaccines led to the attenuation of the M1-polarization of macrophages at early stage,which were marked by de-creased expression of CD16/32 and increased expression of Detectin-1 on cell surface as well as decreased expression of IL-12 and in-creased expression of IL-4 inside the macrophage,in comparison with single vaccine groups,suggesting an interference between the two vaccines.Meanwhile,the activity of CD8+T cells(including the ratio of CD8+CD69+T,CD8+IFN-γ+T and CD8+GranzymeB+T cells) in combined immunization group showed similar tendency to the attenuated phenotypic M1-polarization of macrophages. Conclusion The phenotype of macrophages at the early stage of the co-immunization by Y.pestis and B.bovis vaccines showed consistency with the phenotype and function of CD8+T cells at late stage.It might give us some hint about the possibility of utilizing the phenotypic changes of macrophages to rapidly evaluate the effect of the co-immunization at early stage.

Investigation on antigen-specific T cell responses in type 2 diabetes mellitus patients / 中华内分泌代谢杂志

Objective To investigate the antigen-specific T cell functionality in type 2 diabetes mellitus patients. Methods Peripheral blood from 38 type 2 diabetes mellitus patients and 47 health controls (control group) have been collected. The proportions of CD4+and CD8+T cell as well as the ratio of CD4+/CD8+were monitored by flow cytometry. Meanwhile, antigen- nonspecific and specific Th1 responses were compared between two groups through detecting interferon (IFN)-γ, interleukin 2 (IL-2), and tumor necrosis factor (TNF)-α producing cells upon propylene glycol monomethyl ether acetate (PMA)/ionomycine and epstein-barr virus ( EBV) peptides stimulation, respectively followed by an intracellular cytokine staining. Results Compared to control group, the proportion of CD4+T cell and the ratio of CD4+/CD8+were significantly increased in type 2 diabetes mellitus group (P＜0.05) whereas CD8+T cells exhibited no significant difference between two groups. Antigen-nonspecific Th1 responses in type 2 diabetes mellitus patients were significantly decreased, demonstrated by lower percentages of IFN-γ, IL-2, and TNF-α producing CD4+T cells when compared to control group , while CD8+T cells in type 2 diabetes mellitus patients exhibited similar cytokine production patterns. However, when stimulated by EBV specific peptides, the percentages of IFN-γ, IL-2, and TNF-α producing CD8+T cells were significantly higher in type 2 diabetes mellitus patients than those in control group (P＜0.05). HbA1Cwas positively correlated with the percentage of EBV-specific TNF-α producing CD8+T cells (P＜0.05). Conclusion In type 2 diabetes mellitus, the secretion capacity of CD4+and CD8+T cell was significantly decreased and the antigen-specific responses represent the presence of an abnormal activated status, which indicates that chronic hyperglycemia may damage T cells function and aggravate chronic inflammation.

The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8⁺ T Cells

BACKGROUND: The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8⁺ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8⁺ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8⁺ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis. METHODS: A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software. RESULTS: The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8⁺ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8⁺ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8⁺ T cells (p = .870). CONCLUSIONS: NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8⁺ T cells in acral MM.

Prognostic value of tumor infiltration immune cells in pancreatic cancer / 中华外科杂志

Objective@#To investigate the prognostic effect of tumour-infiltrating immune cell, including CD8+ T cell, regulatory T-cell (Treg) and myeloid-derived suppressor cells (MDSC) on pancreatic patients.@*Methods@#This study retrospectively collected the data of 80 patients who were histologically diagnosed of pancreatic cancer and underwent classical R0 surgical resection at Tianjin Medical University Cancer Institute and Hospital from January 2010 to May 2012. All patients survival were followed up until the cut-off date of January 2015. Clinicopathological features including immunohistochemical staining of FOXP3, CD8 and CD33 were reviewed as indice for evaluating the prognosis of pancreatic patients.The prognostic effect of tumour-infiltrating immune cells were analysed by Kaplan-Meier and Log-rank test. Multiple-factor analysis was conducted with the Cox regression model. The correlation between tumour-infiltrating immune cells and clinicopathological features was analysed by χ2 test. The C57BL/6 mouse model was used to evaluate the efficacy of Treg and MDSC depletion therapy in vivo. Student′s t-test was applied to assess the difference of the tumour volume, Ki-67 positive rate and CD8+ T-cell infiltration proportion between depletion group and control group.@*Results@#Eventually, 80 patients were included and no patient was lost during the follow-up period. The median follow-up time was 33.2 months (7.4-59.9 months). Patients with high level of tumour-infiltrating CD8+ T cells had longer overall survival (OS) time ((21.6±11.9)months vs. (13.6±7.4)months, χ2=4.647, P = 0.031) than those with low level of tumour-infiltrating CD8+ T cells. Tumor infiltration FOXP3+ cells were strongly associated with reduced OS((20.9±8.5)months vs.(13.4±8.8)months, χ2=10.528, P=0.001), reduced relapse free survival (RFS) ((15.2±9.0)months vs. (9.5±8.8)months, χ2=6.288, P=0.012) and larger tumor size(χ2=4.073, r=0.226, P=0.044). The high intratumoural MDSC group showed a significantly shorter OS((23.5±11.8)months vs. (13.8±7.6)months, χ2=5.724, P=0.017), RFS((17.9±11.3)months vs. (10.2±7.5)months, χ2=7.430, P=0.006) and more advanced N stage (χ2=4.714, r=0.243, P=0.030) than the low intratumoural MDSC group. Multivariate Cox analysis revealed that pTNM (P=0.008), tumour-infiltrating Treg density (P=0.009) and intratumoural MDSC density (P=0.034) were independent and negative prognostic factors for OS; pTNM(P=0.003) and tumour-infiltrating MDSC level(P=0.018) were independent and negative factors for RFS. The experiment in vivo revealed that Treg and MDSC depletion therapy significantly decreased tumour volume in the C57BL/6 mouse model of subcutaneous tumours((1 396.3±442.5)mm3 vs. (3 356.9±533.5)mm3, t=4.986, P=0.018). Tumour Ki-67 positive rate significantly decreased (23%±5% vs. 55%±10%, t=3.130, P=0.011) in Treg and MDSC depletion group, whereas, the proportion of tumour-infiltrating CD8+ T cells significantly increased in depletion groups (3.25%±0.69% vs. 0.76%±0.25%, t=3.393, P=0.007).@*Conclusions@#Tumour-infiltrating Treg, MDSC level and pTNM stage are independent prognostic factors for patients with pancreatic cancer. Treg and MDSC depletion therapy can significantly retard tumour growth and increase the level of tumour-infiltrating CD8+ T-cells in the C57BL/6 mouse model of subcutaneous tumours.

Cytotoxic activity in cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) is a chronic disease caused by species of the protozoan Leishmania and characterised by the presence of ulcerated skin lesions. Both parasite and host factors affect the clinical presentation of the disease. The development of skin ulcers in CL is associated with an inflammatory response mediated by cells that control parasite growth but also contribute to pathogenesis. CD8+ T cells contribute to deleterious inflammatory responses in patients with CL through cytotoxic mechanisms. In addition, natural killer cells also limit Leishmania infections by production of interferon-γ and cytotoxicity. In this review, we focus on studies of cytotoxicity in CL and its contribution to the pathogenesis of this disease.

Changes of CD3 +CD8 +T cells and its relationships with markers of inflammation and humoral immu-nity in children with severe bacterial meningitis / 中国小儿急救医学

Objective To explore the role of CD3 +CD8 +T cells in children with severe bacterial meningitis at early stage by studying the changes of CD3 +CD8 +T cells and its relationships with markers of inflammation and humoral immunity. Methods Thirty-nine cases aged ≤14 years old were enrolled in this retrospective study,who were admitted in our PICU from Aug 1. 2014 to Dec 31. 2015 with diagnosis of se-vere bacterial meningitis. The patients were divided into 2 groups according to the changes of CD3 +CD8 + T cells:group A:normal or elevated(≥190/mm3,n=22),group B:decreased( 80% was more than 7 cases(31. 8%) in group A,there were significant differences(P<0. 05). Fourteen cases(82. 3%) with glucose concentration lower than 2. 0 mmol/L in group B was more than 11 cases (50. 0%) in group A,the difference was significant(P<0. 05). Conclusion CD3 +CD8 +T cells might be suppressed in children with severe bacterial meningitis at early stage,and might associate to the damaging de-gree of brain,inflammation reaction and prognosis in those patients,which should be helpful in using of im-mune regulators for children with severe bacterial meningitis.

Study on quantity and function of CD8+T cells in patients with repeated implantation failure / 实用医学杂志

Objective To investigate the quantity and function of CD8+T cells in peripheral blood of pa-tients with repeated implantation failure(RIF).Methods Thirty-seven patients with RIF and 19 healthy controls were enrolled in this study.The peripheral blood and endometrium were collected during the mid-luteal phase.The percentage of peripheral CD8+T subsets and the levels of perforin and granzyme B of peripheral CD8+T cells were determined by flow cytometry assay.The percentage of endometrial CD8+T cells was detected by IHC,the produc-tion of perforin and granzyme B of endometrial CD8+T cells was detected by IF. Results Compared with the con-trol group,the percentage of peripheral CD8+T cells in patients with RIF was not significantly changed(37.22% vs. 37.15%,P>0.05).However,the porportion of endometrial CD8+T cells in the RIF group was higher than that in the control group(1.99% vs.3.77%,P<0.001).The levels of perforin and granzyme B in peripheral blood and en-dometrial CD8+T cells in patients with RIF were similar with those in the control group.Conclusions Compared to the control group,the percentage of endometrial CD8+T was markedly upregulated in patients with RIF.However, the production of perforin and granzyme B were similar between the control group and the RIF group.

Detection of HIV-specific T cells and their subsets expressing CD160 in peripheral blood of asymptomatic HIV-infected patients / 中华实验和临床病毒学杂志

Objective@#To investigate the expression of CD160 in HIV-specific T cells and their subsets in peripheral blood of asymptomatic human immunodeficiency virus (HIV) infected individuals.@*Methods@#A total of 43 asymptomatic HIV-infected individuals without antiretroviral therapy (ART) and 18 healthy controls were recruited from the No. 302 Hospital of PLA between June 2014 and November 2015. Peripheral blood mononuclear cells (PBMC) were isolated from peripheral bloods of these subjects. CD160 was stained with fluorescent antibody. Expression of CD160 in HIV-specific T cells and their subsets was detected by flow cytometry.@*Results@#The frequency and median fluorescence intensity (MFI) of CD160 on the whole HIV-specific CD4+ T cells and CD8+ T cells were higher than those in the healthy controls(P<0.01). In subsets of HIV-specific CD4+ T cells, the MFI of CD160 in CD4+ Tn cells and CD4+ Teff cells, and the frequency of CD160 in CD4+ Teff cells were significantly increased (P<0.01). CD8+ Tn fine, CD8+ Tcm cells and CD8+ Tem cells showed a significant upregulation in the frequency and MFI of CD160 (P<0.01).@*Conclusions@#Chronic HIV infection can lead to high expression of CD160 in HIV-specific T cells and their different subsets, causing cellular immune dysfunction, which may further impair the ability to control the HIV virus.

Liver sinusoidal endothelial cells regulate adaptive immune tolerance in the liver / 中华肝脏病杂志

Liver sinusoidal endothelial cells are a major group of nonparenchymal cells in the liver and are involved in immunological surveillance of the liver through the expression of various scavenger receptors and pattern recognition receptors. However, in case of several physiological states, viral infections, and tumor environment, liver sinusoidal endothelial cells maintain immune tolerance in the liver through various mechanisms and cause persistent viral infection and tumor metastasis. This article reviews the mechanisms of immune tolerance of CD4 + T cells and CD8 + T cells in the liver induced by liver sinusoidal endothelial cells.