The role of Lyt-2+ T cells in the regulation of autoimmunity in murine lupus.
Systemic lupus erythematosus (SLE) in humans and in mice is characterized by reduced suppressor T-cell activity. This observation suggests that selective loss or impaired function of suppressor T cells may contribute to the development of autoimmunity. To clarify the role of suppressor T cells in the pathogenesis of SLE, we used a rat MAb to selectively deplete Lyt-2+ ('suppressor/cytotoxic') T cells from lupus-prone NZB/NZW F1 (B/W) mice. Treatment consisted of weekly intraperitoneal injections of anti-Lyt-2 (2 mg/mouse) beginning at age 4 months, prior to the onset of overt clinical illness. Control mice received weekly injections of either non-immune rat IgG or saline. Despite sustained depletion of Lyt-2+ T cells, mice treated with anti-Lyt-2 were indistinguishable from control mice with respect to production of anti-DNA antibodies, development of renal disease, and mortality. These findings imply that Lyt-2+ T cells do not regulate autoimmunity in B/W mice. However, they do not exclude the possibility that Lyt-2+ T cells suppress autoimmunity in normal mice but are simply non-functional in B/W mice. Therefore, we also examined the consequences of depleting Lyt-2+ T cells from non-autoimmune C57BL/6 x NZW (B6/NZW) mice. Depletion of Lyt-2+ T cells from B6/NZW from age 4 to 10 months produced neither serologic nor clinical evidence of murine lupus. These observations suggest that suppressor T cell defects are not sufficient to cause murine lupus.
Wofsy
D
D
Arthritis/Immunology Section, Veterans Administration Medical Center, San Francisco, California.
D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000276:immunology*; D004247:DNA / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007518:Isoantibodies; C029805:Lyt antibodies; D004247:DNA