Propagation and regulation of systemic autoimmunity by gammadelta T cells.

Abstract

Although many studies have demonstrated a pathogenic role for alphabeta T cells in murine lupus, little work has addressed gammadelta T cells. Here, the roles of alphabeta and gammadelta T cells in the pathogenesis of systemic autoimmunity were investigated by generating lupus-prone mice deficient in alphabeta T cells and/or gammadelta T cells. Mice deficient in gammadelta T cells developed an exacerbated disease phenotype compared with that of T cell-intact mice, consisting of augmented hypergammaglobulinemia and autoantibody production, more severe renal disease, and increased mortality, associated with a polyclonal expansion of conventional CD4+ alphabeta T cells. Conversely, alphabeta T cell-deficient animals developed a partial lupus syndrome, characterized by isotype-specific hypergammaglobulinemia, incompletely penetrant autoantibodies, and mild immune complex renal disease, all of which were driven by gammadelta T cell-dependent help. These data indicate that gammadelta T cells participate in both the regulation and the propagation of murine lupus.