Autoreactive T cell clones from patients with systemic lupus erythematosus support polyclonal autoantibody production

This work examines the functional properties and TCRbeta gene utilization of 15 autoreactive T cell clones derived from five patients with systemic lupus erythematosus. All these clones proliferated and secreted cytokine when stimulated in vitro by autologous (but not allogenic) B cells. Individual T cell clones used diverse TCRbeta genes and did not show skewing toward the preferential usage of anionically charged receptors. Autoreactive T cell clones supported polyclonal B cell activation, as characterized by the production of anti-DNA, anti-Sjögren syndrome A, and anti-tetanus toxoid (anti-TT) Abs. This T cell help was mediated through the production of immunostimulatory cytokines, especially IL-6. Although stimulation of the autoreactive clones was blocked by anti-HLA class II Abs, the T cell clones did not proliferate, nor did they support polyclonal IgG production by HLA class II-matched normal B cells. Unlike the autoreactive clones, TT-specific clones derived from the same patients provided help selectively to B cells secreting anti-TT Abs. These findings suggest that autoreactive T cells from systemic lupus erythematosus patients are triggered to provide help following cognate interactions with self-peptides presented in the context of HLA class II molecules expressed on autologous B cells regardless of their specificities.