Induction of autoimmune phenomena in normal mice treated with natural thymocytotoxic autoantibody

Abstract

Natural thymocytotoxic autoantibody (NTA) developed spontaneously in New Zealand Black (NZB) mice consists of two autoantibodies in terms of target cell specificity. One of the autoantibodies, NTA-2, is strongly cytotoxic only against desialized lymphocytes, whereas the other one, NTA-1, is cytotoxic against both intact thymocytes and asialolymphocytes. To study the pathogenic role of NTA in murine autoimmunity, DBA/2 mice were injected every other day with affinity-purified NTA (NTA-1, NTA-2). Control mice received normal mice sera (NMS) or saline. After 20 days of treatment, spleen cells from DBA/2 mice treated with NTA-1 or NTA-2 showed a significant increase in the number of anti-ssDNA plaque-forming cells and IgM-producing cells. Sera from NTA-treated mice showed greater DNA binding than sera from control mice did. The levels of proteinuria were moderately increased in NTA-2-treated mice. Con A responsiveness of thymocytes was markedly reduced in NTA-2-treated mice. On the other hand, Con A-activated spleen cells from both control and NTA-treated mice equally suppressed anti-SRBC antibody production in vitro, suggesting that NTA treatment didn't affect the direct precursors of suppressor T cells. Finally, prior absorption of NTA-1 by thymocytes prevented its ability to induce anti-DNA antibodies; however, prior absorption of NTA-2 by thymocytes didn't affect its activity.