Manipulation of immune regulation in systemic lupus erythematosus.

Production of autoantibodies by B cells in systemic lupus erythematosus (SLE) can be interrupted via induction of regulatory and suppressor T cells. We have used the strategy of tolerizing lupus-prone (NZBxNZW)F(1) mice with an artificial peptide based on sequences common to several anti-double stranded (ds)DNA antibodies to induce regulatory and suppressor T cells that block production of anti-DNA antibodies and prolong their survival. At least one type of suppressor T cells (CD8+) and one type of regulatory T cell (CD4+ expressing the IL-2 receptor alpha chain CD25) are raised under this condition. While CD8+ suppressors (TS) require soluble factors to block help of T cells to B cells, regulatory CD4+CD25+ T cells (TR) curb the production of anti-DNA antibodies from B cells via cell contact through molecules that include membrane-bound TGFbeta and GITR. Moreover, CD8+ suppressors seem to act independently on antigen specificity, while TR act in an antigen-specific fashion. We hypothesize that the differences between these two lymphocyte subsets that share the common ability to dampen production of autoantibodies might underlie significant temporal and teleological advantages for optimal control of autoimmune reactivity.