Human double-negative T cells in systemic lupus erythematosus provide helpfor IgG and are restricted by CD1c

To understand the mechanism of T cell help for IBG production in systemic l upus erythematosus (SLE) we investigated the response of CD4- and CD8-negat ive (double-negative (DN)) T cells because: 1) DN T cells are present at un usually high frequency in patients with SLE and can induce. pathogenic auto antibodies; 2) the DN T cell repertoire includes cells restricted by CD1 Ag -presenting molecules; and 3) CD1c is expressed on a population of circulat ing B cells. We derived DN T cell lines from SLE patients and healthy indiv iduals. In the presence of CD1(+) APCs, DN T cell lines from SLE patients p roduced both IL-4 and IFN-gamma, whereas DN T cells from healthy donors pro duced IFN-gamma, but no IL-4, In general, cells from patients with highly a ctive disease produced high levels of IFN-gamma; cells from those with litt le activity produced high IL-4, Coculture of CD1c-directly reactive T cells from healthy donors with CD1c(+) B cells elicited IgM Abs, but little or n o IgG, In contrast, CD1c-directly reactive T cells from SLE patients induce d isotype switching, with a striking increase in IgG production. Neutralizi ng Abs to CD1c inhibited the ability of DN T cells to induce IgG production from CD1c(+) B cells, further indicating that CD1c mediated the T and B ce ll interaction. IgG production was also inhibited by neutralizing Abs to IL -4, correlating with the cytokine pattern of TPN T cells derived from these patients. The data suggest that CD1c-restricted T cells from SLE patients can provide help to CD1c(+) B cells for IgG production and could therefore promote pathogenic autoantibody responses in SLE.