Study Of T Cell Subsets And Their Functions In The Pathogenesis Of Systemic Lupus Erythematosus

Objective:Systemic lupus erythematosus(SLE)is a potentially fatal chronic autoimmune disease most commonly seen in women from adolescence to menopause.It is characterized by an imbalance in the tolerance mechanisms of the autoimmune system,immune dysfunction,and the production of large amounts of autoantibodies by the body.The immune complexes are deposited in several tissues and organs,producing pathological damage to the body.The pathogenesis of the disease is complex and the immune dysfunction in SLE patients includes the production of auto-reactive T cells and auto-antibodies by highly reactive B cells.Various studies have also shown that T-cell function is abnormal in SLE patients and may play an important regulatory role in autoantibody production.In this study,we used BXSB/Yaa lupus-like mouse model to detect the number,activation,cytokine secretion and expression of effector molecules of CD4+ T and CD8+ T cell subsets in spleen and kidney by flow cytometry(FCM)to investigate the role of T cell subsets(CD4+,CD8+)in SLE and their related mechanisms of action,so as to further explore the pathogenesis of SLE and provide new ideas for the treatment of SLE.Method:The BXSB/Yaa mouse lupus model was used as the study object.3-month-old and6-month-old BXSB mice were selected,spleens and kidneys were removed,and lymphocytes were isolated.Flow cytometry was used to detect the proportion of lymphocyte subpopulations in the spleen of mice to assess the function and immunophenotype of CD4+ and CD8+ T cells and the expression of cytokines,and to analyze the changes of cytokines in the pathogenesis of SLE mice model to further reveal the pathogenesis of SLE.The kidneys were stained with hematoxylin-eosin staining(HE)to observe the pathological changes in the kidneys of mice at different months of age.Streaming data analysis was performed using FlowJo software(Version 10.5.3),using the Graph Pad Prism program(Graph Pad 8.0)for statistical analysis.Result:1.In the BXSB/Yaa mouse model,the proportion of CD8+ T cells was significantly decreased in older mice compared to younger mice.2.The proportion of CD4+CD44+ and CD8+CD44+ T was significantly increased in the spleen and kidney of older mice.3.The proportion of TNF-α secreted by CD4+ T cells and CD8+ T cells was increased and IFN-r was downregulated in the spleen of older mice;IL-2 secreted by CD8+ T cells was increased;Fas L expression was upregulated on CD8+ T cells;PD-1expression was increased on CD8+ T cells.4.Renal injury was significantly increased in older mice at monthly age.Conclusion:1.CD4+ T cells and CD8+ T cells play an important role in the BXSB/Yaa mouse model.2.T-cell activation and an increase in the proportion of effector T cells are involved in the development of SLE.3.The secretory function of T cells is altered,and effector molecules on CD8+ T cells are highly expressed.There may be depletion during the progression of SLE.4.Renal damage in BXSB mice increases with age.