Propagation and regulation of systemic autoimmunity by gammadelta T cells.
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.
Peng
S L
SL
Department of Biology, Yale University, New Haven, CT 06510, USA.
Madaio
M P
MP
Hayday
A C
AC
Craft
J
J
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013154:Spleen / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D016207:Cytokines; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta