| Systemic lupus erythematosus(SLE) is a kind of autoimmune diseases,which characterized by immune abnormalities in systemic organs.The etiology and pathogenesis of SLE is still not completely clear now. The risk factors that have a possible correlation with SLE may include heredity infection,environment,sex hormone and drug. Corticosteroid and immunosuppressive agents are still the main drug therapy. However, long-term applications of these drugs to patients often have serious adverse reactions.Indicators of the observation of disease activity and severity main include clinical manifestations,blood and urine regular tests,ESR,autoantibodies and SLEDAI scores. However, the above efficacy variables reflect the effectiveness of medicinal treatment and the activity of the disease from the damage and recovery of the target organs,which can not reflect the the role of human lymphocytes of that.Usefull indicators in the observation of disease activity and the clinical use have not yet been available,which will be further studied in pathogenesis level.Therefore, to explore effective indicators for disease activity, clear the synergistic effect and the further pathogenesis of SLE, modificate the treatment programs and find new treatments to reduce the serious adverse reactions, it is still very necessary,and become the greatest aspiration of Clinicians and researchers.Previous studies have demonstrated that SLE has a relationship with humoral and cellular immunological abnormalities. Abnomal functions of T lymphocytes promoting the actiation of B lymphocytes helps to produce large numbers of autoantibodies, formulate immune complex(IC) and activate the complement. And the results of clinical manifestations are multi-organ impairrment. Among the abnomal immune response,the imbalance of T cell function plays a very important part, which is the initial step of the pathogensis of SLE. Whether lpr mice or patients with SLE, the absence of immune tolerance of T cell is an important pathogenic factor, however, the concrete machanism is not very clear.Regulatory T cells, a subpopulation of T cells,have specific immunosuppressive function,which may an play important role in autoimmune disease,organ transplantation,Antitumor Immune,chronic Inflammatory reaction and persistent-infection.Regulatory T cells possessing the properties of immunosupprcssion and anergy depress the activation of Regulatory T cell and B cell and the production of cytokines to avoid the onset of autoimmune diseases.Tr1,Th3 and CD4+CD25+ Treg are the most commonly researched regulatory T cell. CD4+CD25+Treg are thought to be the most important group among Treg family; Foxp3 is conceived as the special marker, which play a vital role in the production and function of regulatory T cells.The disorder of quantity and function of Foxp3 have close relationship with the development of SLE.Normally,the proliferative response to the outside stimulus of the effector T cells can be inhibited reversely. Regulatory T cells may control the activation and proliferation of self reactive T cells by the body's active mode. Deficiencies and defect on function of these cells can affect the stablization of autoimmune environment and cause autoimmune diseases thereby.As everyone knows, cytokines have complex interaction relationship. In vivo, cytokines participate in a wide range of immune regulation in a form of network. Many studies had show that, the imbalances of cytokines may play an important role in the pathogenesis of systemic lupus erythematosus.Studies in vitro show that the functionof regulatory T cells may has a relationship with direct contact with cells between each other. Studies in vivo show that the inhibit functin of regulatory T cells are dependent on the participation of some cytokines,such as TGF-β1,IL-6,IL-10,IFN-y and so on.IL-6 is a kind of cytokines with multiple immune adjustment functions,which can be produced by T lymphocytes, monocytes, vas-cuiar endothelial cells, fibroblast and some tumor cells. The level of IL-6 is increased in patients with acute inflammation,autoimmune diseases and T lymphocyte malignances(multiple myeloma,for example).TGF-β1 is synthesized and released by the activated T cells,B cells and macrophage,the same as some tumor cells,osteogenic cells and endothelial cells. TGF-β1 is a kind of growth factor not only in anti-inflammatory activity but also in healing-promoting effects,which broadly participate in Interaction Between immune system.The function of regulatory T cells and cytokines arosen in the SLE, which as one of classic autoimmune disease,-has arosen widely attention of domestic sociology scholars. The role of regulatory T cells and cytokines in the course of treatment is becoming the research hotspot in the world. The mechanism and interrelation of regulatory T cells and cytokines in the SLE is still unknown. So further researches into the expression level and clinical significance of CD4+CD25+ Foxp3+Treg and cytokines in SLE patients may exert positive effects on the elucidating the pathogenesis of SLE and devising new targeting therapy.ObjectiveTo investigate the proportions of CD4+CD25+Treg and CD4+CD25+ Foxp3+Treg in peripheral blood and the levels of cytokines(IL-6 and TGF-β1)in systemic lupus erythematosus and normal controls, analyze the relationship of the expression of CD4+CD25+Foxp3+Treg and IL-6 in the peripheral blood with SLE disease active indices, then to explore the role of regulatory Tcells and cytokines in the pathogenesis of SLE.MethodsA total of fifty four SLE patients(including thirty one active and tweenty-five remissive)and twenty normal controls were selected. Flow-cytometric assay was employed for detection of the proportions of CD4+CD25+Treg and CD4+CD25+ Foxp3+Treg in CD4+T cells in the peripheral blood of SLE.And double antibody sandwich ELISA was applied to detect cytokines of IL-6 and TGF-β1 in the serum from the peripheral blood of SLE patients and normal controls. The interaction and association between the proportions of peripheral blood regulatory T cells and the levels of eytokines were analyzed.Results1,It was showed by flow cytometry that the percentage of CD4+CD25+Treg in the CD4+Tcells from patients with active, inactive SLE and controls was 4.0515 %±2.39635%,6.1829%±2.35146%,7.9593%±3.42551%.The percentage of CD4+CD25+Treg in active SLE patients were significantly lower than those of inactive SLE and healthy controls (p=0.03,0.000,respectively); and there was no significant differences in the percentage of CD4+CD25+T cell between inactive SLE and healthy controls(P>0.05).2,The percentage of CD4+CD25+Foxp3+Treg in the CD4+Tcells from patients with active, inactive SLE and controls was 2.1597%±1.12888%,5.1603%±1.65242%,6.1687%±3.4745%. The percentage of CD4+CD25+Foxp3+Treg in active SLE patients were significantly lower than those of inactive SLE and healthy controls (p=0.000,0.000,respectively); and there was no significant differences in the percentage of CD4+CD25+Foxp3+Treg between inactive SLE and healthy controls(P>0.05).3,The percentage of CD4+CD25+Foxp3+Treg were negative correlated with SLEDAI scores (r=-0.636, P=0.000),but the percentage of CD4+CD25+Treg had no correlated with SLEDAI scores (P>0.05).4,The concentration of IL-6 in patients with active,inactive SLE and controls was 36.61±9.73 (ng/ml),28.24±4.69 (ng/ml),22.37±5.60 (ng/ml).Serum concentration of IL-6 is significantly increased in both the active and inactive SLE groups as compared with normal control group (P=0.007,0.000, respectively), while the serum IL-6 in the active SLE group was significantly higher than in the inactive SLE group (P=0.015).5,The concentration of serum TGF-β1 in active SLE patients were significantly lower than those of inactive SLE and healthy controls(p=0.005,0.000,respectively); and there was no significant differences in the concentration of serum TGF-β1 between inactive SLE and healthy controls(P>0.05).6,The level of serum IL-6 was positive correlations with SLEDAI scores(r=-0.532,P=0.001),and had negative correlations with CD4+CD25+Treg (r=-0.636, P=0.000), but had little correlations with CD4+CD25+Foxp3+Treg (r=-0.372, P=0.008).7, The level of serum TGF-β1 had negative correlations with SLEDAI scores(r=-0.663,P=0.000), and had slight positively correlated with the percentage of CD4+CD25+Treg and CD4+CD25+Foxp3+Treg (r=0.426,0.300, respectively, P<0.05).Conclusions1,These results demonstrate that deficien of CD4+CD25+Treg and CD4+ CD25+Foxp3+Treg may play an important role in the pathogenesis of SLE.2,The percent of CD4+CD25+Foxp3+Treg can more sensitively reflect the disease activity level of SLE than the percent of CD4+CD25+Treg.3,Increase the quantity of Treg may provides a new approach to treat the patient of SLE.4,The increase of IL-6 and the decrease of TGF-β1 may cause the reduce of the percentage of CD4+CD25+Treg and CD4+CD25+Foxp3+Treg in SLE.5,The change of concentration of IL-6 and TGF-β1 may play an important role in the pathogenesis of SLE.6,Correct of the concentration of serum IL-6 and TGF-β1 may Brings new direction for treatment of SLE. |
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