ABSTRACT
Immune-mediated dermatoses are the skin diseases caused by the breakdown of immune tolerance,including lupus erythematosus and dermatomyositis.The imbalance between regulatory T cells (Tregs) and effector T cells (Teffs) plays a key role in the pathogenesis of these diseases.Low-dose interleukin-2 can preferentially activate Tregs and reverse the imbalance between Tregs and Teffs to recover the immune tolerance,which has attracted attention in the treatment of immune-mediated dermatoses.This review summarizes the research progress in the immunomodulatory mechanism and clinical application of low-dose interleukin-2 in immune-mediated dermatoses,providing a new idea for the clinical treatment of these diseases.
Subject(s)
Humans , Interleukin-2 , Lupus Erythematosus, Systemic , T-Lymphocytes, Regulatory , Skin Diseases/drug therapyABSTRACT
Objective To investigate the role of miR-10a in CD4+CD25+Treg-mediated immunosuppression during sepsis and its potential role in immunotherapy for sepsis.Methods Sepsis mouse model was established by cecal ligation and puncture(CLP).Balb/c mice of clean grade were sacrificed 1,3,5,and 7 days after operation.Blood as well as spleen samples were harvested at given intervals.The splenic CD4+CD25+Treg cells and CD4+T cells were isolated by MACS microbeads.Cells were cultured,and phenotypes were analyzed by flow cytometry.The miR-10a expressed in Treg cells were detected by Real-time PCR.After administration of LV-mmu-miR-10a-5p-inhibition,the immunosuppressive function have been detected.Statistical analyses were performed using one-way analysis of variance (SPSS 19.0,Chicago,USA) test followed by Dunnett-t test to compare among three or more groups or by Student's t-test to compare between two groups.Results The percentages of splenic Tregs (CD4+CD25+/CD4+T) was (7.34±1.2)％ in normal group,and the increase in percentage of Tregs in spleen has been observed in septic mice (P＜0.05).The mean fluorescence intensity (MFI) of Foxp3+Treg was increased in septic mice compared with sham group (P＜0.05).The expression of miR-10a was significantly elevated on CLP 1-7 day (P＜0.05).After down-regulation of miR-10a in septic mice,the percentages of Tregs (CD4+CD25+/CD4+T) was significantly increased in septic mice (P＜0.05),the MFI of Foxp3+Treg was increased in septic mice compared with control group (P＜0.05).The CD4+T cell proliferative activity in CLP-induced mice was significantly suppressed on CLP 3 day compared with sham group (P＜0.05).After down-regulation of miR-10a in septic mice,the CD4+T cell proliferative activity was significantly suppressed compared with control group (P＜0.05).Conclusions Treg plays a critical role in immunosuppression in septic mice.Inhibition of miR-10a in vivo could enhence immunesuppression of CD4+CD25+Treg.Therefore miR-10a may participate in the regulation of CD4+CD25+Treg immunosuppression in sepsis and become the target for immunotherapy.
ABSTRACT
CD8+ T cells play an essential role in defending against viruses,intracellular bacteria,protozoal infections and clearance of tumors since almost all the nucleated cells express MHCⅠ molecule.Following antigen recognition,CD8+ T cells are activated and differentiated to different subsets of effector or memory cells,which could clear the pathogen and form long-term protection.Phenotypic markers,functional properties and anatomical locations are different among these CD8+ T cell subsets.They also show variation in surviving time,proliferation and effector functions when re-challenged with the pathogen or tumor.Multiple signaling pathways and transcriptional factors are involved in CD8+ T cells activation and differentiation,and will be discussed in this review.We will also briefly summary the clinical applications of T cells against tumor or pathogens.
ABSTRACT
Objective To investigate the influence of murine cytomegalovirus on the expansion of CD+CD25+ Foxp3+ regulatory T cell (Treg) and the activation of CD4+ CD25+Foxp3 - effector T cell (TE) in vivo. Methods Forty-two BALB/c mice were intraperitoneally inoculated with appropriate amount ofMCMV Smith strain for establishing the model of infection, another 42 mice served as mocked-infected con-trois. Day 28 post MCMV infection was determined to be the demarcation point of the acute and chronic in- fection based on the viral load of major visceral organs. On day 1,3, 7, 14, 28, 45 and 60 post infection, splenocytes were prepared by means of routine method. The proportions of CD4+CD25+ Foxp3+Treg and CD4+CD25+Foxp3- activated TE in T lymphocyte were measured by flow cytometry. Results The propor- tion of CD+CD25+ Foxp3+ T cells in T lymphocytes was persistently suppressed since day 7 post infection, and fell to the lowest level on day 28 post infection (P <0.01), then zoomed and reached the peak value on day 60 post infection (P < 0.05). CD4+CD25+ Foxp3 - TE proportion was up to the highest on day 3 post infection(P < 0. 01), then suppressed and in significantly lower level since day 45 post infection (P < 0.05). Treg/CD+TE ratio was in lower level on day 3 to 14 post infection(P <0.05) ; but on day 45 and day 60 post infection Treg/CD+ TE ratio was markedly increased (P < 0.05). Conclusion MCMV infec- tion can increase the CD+CD25+Foxp3+ Treg proportion, and inhibit CD4+T cells activation in chronic in- fection phase, which is likely to suppress the function of antiviral immunity in the infected host to cause a persistent latent infection.
ABSTRACT
OBJECTIVE: The aim of this study is to verify the hypothesis that human dendritic cells(DCs) can process antigens from glioma cell apoptotic bodies and induce antigen-specific effector T cells. METHODS: DCs generated in the presence of granulocyte macrophage-colony stimulating factor(GM-CSF) and interleukin-4(IL-4) from peripheral blood mononuclear cells(PBMCs) of healthy donors with human leucocyte antigen(HLA) A*0201 were cultured for 7 days. Glioma apoptotic bodies(GABs) from T98G glioblastoma cells following 18 hour-actinomycin D treatment were co-incubated with DCs for 3 days. CD8 T cells isolated from peripheral blood of same donors were cultured in media containing IL-2 and were stimulated by GAB-pulsed DCs three times at a weekly interval. The interferon-gamma(IFN-gamma), a cytokine related to cytotoxicity, concentrations of cell culture supernates were measured by enzyme immunoassay technique. RESULTS: Induced DCs had DC's own phenotypic characteristics such as highly expressed major histocompatibility complex(MHC) class II, CD1a and CD86 molecules. They also had high endocytotic activity. Preteatment of T98G glioma cells with actinomycin D resulted in 53% of cells undergoing apoptosis. IFN-gamma production of effector T cells stimulated by GAB-pulsed DCs was significantly higher than that of T cells stimulated by non-pulsed DCs. CONCLUSION: Naive CD8 T cells can be activated by human GAB-pulsed DCs to become antigen-specific effector T cells. Using GABs as a antigen source may be a novel approach in future DC-based immunotherapeutic trials for malignant glioma.