PROPAGATION AND REGULATION OF SYSTEMIC AUTOIMMUNITY BY GAMMA-DELTA T-CELLS

Although many studies have demonstrated a pathogenic role for alpha be ta T cells in murine lupus, little work has addressed gamma delta T ce lls. Here, the roles of alpha beta and gamma delta T cells in the path ogenesis of systemic autoimmunity were investigated by generating lupu s-prone mice deficient in alpha beta T cells and/or gamma delta T cell s. Mice deficient in gamma delta T cells developed an exacerbated dise ase phenotype compared with that of T cell-intact mice, consisting of augmented hypergammaglobulinemia and autoantibody production, more sev ere renal disease, and increased mortality, associated with a polyclon al expansion of conventional CD4(+) alpha beta T cells. Conversely, al pha beta 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 gamma delta T cell-dependent help, These data indicate that gamma delta T cells participate in both the regulation a nd the propagation of murine lupus.