AUTOREACTIVE T-CELL CLONES FROM PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS SUPPORT POLYCLONAL AUTOANTIBODY PRODUCTION

This work examines the functional properties and TCR beta gene utiliza tion of 15 autoreactive T cell clones derived from five patients with systemic lupus erythematosus. All these clones proliferated and secret ed cytokine when stimulated in vitro by autologous (but not allogenic) B cells. Individual T cell clones used diverse TCR beta genes and did not show skewing toward the preferential usage of anionically charged receptors. Autoreactive T cell clones supported polyclonal B cell act ivation, as characterized by the production of anti-DNA, anti-Sjogren syndrome A, and anti-tetanus toroid (anti-TT) Abs. This T cell help wa s mediated through the production of immunostimulatory cytokines, espe cially IL-6. Although stimulation of the autoreactive clones was block ed by anti-HLA class II Abs, the T cell clones did not proliferate, no r did they support polyclonal IgG production by HLA class II-matched n ormal B cells. Unlike the autoreactive clones, TT-specific clones deri ved from the same patients provided help selectively to B cells secret ing anti-TT Abs. These findings suggest that autoreactive T cells from systemic lupus erythematosus patients are triggered to provide help f ollowing cognate interactions with self-peptides presented in the cont ext of HLA class II molecules expressed on autologous B cells regardle ss of their specificities.