Expansion of IL-7Ralow memory CD8 T cells in human lupus (101.19)

Abstract

Abstract Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disorder that is characterized by production of autoantibodies and immune complex deposition. In the immunopathogenesis of SLE, CD4+ T cells play as critical drivers of B cell dependent autoantibody response, but little is known about the role of CD8+ T cells in the development of SLE. Recent studies have shown that the expansion of memory CD8+ T cells occurs in SLE patients. We have measured the expression of IL-7 receptor alpha (IL-7Ra, CD127) on memory CD8+ T cells in SLE patients, since IL-7 and IL-7R are involved in homeostasis of CD8+ T cells. As previous reported, we found two subsets expressing high and low levels of IL-7Ra on memory CD8+ T cells in SLE patients and healthy controls. In this study, we showed that SLE patients have an increased frequency of IL-7Ralow memory CD8+ T cells compared to healthy controls. This cell subset expresses high levels of cytotoxic molecule perforin with the capacity to damage tissue. Furthermore, the frequency of IL-7Ralow memory CD8+ T cells correlated with disease activity as measured by SLE disease activity index (SLEDAI). Although T cell receptor triggering barely induced IL-7Ralow cell proliferation, the homeostatic cytokine IL-15 substantially induced the proliferation of this cell subset. Our findings suggest a potential role for IL-7Ralow memory CD8+ T cells in the development of SLE.