Role of CD4^+CD28^-T cell subset in patients with Systemic Lupus Erythematosus

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Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and defects of immunoregulatory T cells. CD28 antigen is an accessory molecule, that transduces a potent costimulatory signal for cell activation, and is expressed on the vast majority of CD4_+ T cells. It has been reported that CD4_+CD28_- T cells were refractory to anergy induction and showed sustained reactivity to the self antigen, suggesting involvement of CD4_+CD28_- T cells in the pathogenesis of autoimmune diseases. We found that CD4_+ CD28_- T cells are prevalent in peripheral blood in patients with SLE.This T cell subset expressed HLA-DR,IL-2 receptor, VLAbeta chain brightly, indicating that this subset locates in a late stage of T cell activation cascade. We found that CD4_+ CD28_- T cells exhibited oligoclonal expansion of the selected clones. In addition, CD4_+ CD28_- T cells produced large amounts of IL-6 spontaneously. These results suggest that SLE CD4_+CD28_- T cells have been activated by unidentified, possibly self, antigen in vivo and participate in the pathogenesis of human SLE.