The Role of Cd4(+)Cd25(+) T Cells in Autoantibody Production in Murine Lupus

Abstract

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by the loss of tolerance to self-antigen. Because it is currently not known if regulatory T (T-reg) cells are involved in the pathogenesis, we determined the frequency of CD4(+)CD25(+) T cells and assayed the related gene expression levels in CD4(+)CD25(+) T cells isolated from both lupus mice (NZB/NZW F-1) and normal control mice (DBA2/ NZW F-1). The results showed that the frequency of CD4(+)CD25(+) T cells in lupus mice was lower than that of normal mice. Except for the high expression level of interleukin (IL)-10 mRNA, CD4(+)CD25(+) T cells from lupus mice expressed normal forkhead box P3 ( Foxp3) and transforming growth factor (TGF)-beta mRNA, and exerted suppressive functions. Furthermore, we depleted CD25 (+) T-reg cells of non-autoimmune mice with anti-CD25 antibody and broke their tolerance with apoptotic cell- pulsed dendritic cells for the follow-up of autoantibody levels. The mice in the CD25(+) cell-depleted group had higher titres of anti-double-strand/single -strand DNA antibodies than those of the isotype control antibody- treated group. These findings indicated that CD4(+)CD25(+) T cells might be involved in the regulatory mechanism of autoantibody production.