Propagation and Regulation of Systemic Autoimmunity by γδ T Cells

Although many studies have demonstrated a pathogenic role for αβ T cells in murine lupus, little work has addressed γδ T cells. Here, the roles of αβ and γδ T cells in the pathogenesis of systemic autoimmunity were investigated by generating lupus-prone mice deficient in αβ T cells and/or γδ T cells. Mice deficient in γδ 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⁺ αβ T cells. Conversely, αβ 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 γδ T cell-dependent help. These data indicate that γδ T cells participate in both the regulation and the propagation of murine lupus.