Preferential lysis of undifferentiated thymocytes by natural thymocytotoxic antibodies from New Zealand black mice

Autoimmune NZB mice spontaneously develop auto-antibodies to thymus-dependent lymphocytes. These naturally occurring thymocytotoxic antibodies (NTA) were studied for their ability to lyse, in vitro, thymocytes undergoing Con A-induced in vitro proliferation and thymocytes undergoing natural in vivo differentiation. NTA were preferentially cytolytic for immature thymocytes. Thymocytes stimulated with Con A for 48 hr were less susceptible to lysis by NTA than were control thymocytes pulsed with Con A for 5 min. Conversely, thymocytes stimulated with Con A for 48 hr were more susceptible to lysis by anti-H-2 antibodies than were control thymocytes pulsed with Con A for 5 min. In addition, when thymocytes were fractionated by peanut agglutinin (PNA), the PNA (+) fraction (immature thymocytes) was more readily lysed by NTA than was the PNA (-) fraction (maturing thymocytes). These results suggest that NTA may play a role in the development of autoimmunity in NZB mice by sequentially eliminating thymus-dependent lymphocytes on the basis of the quantity of NTA-reactive antigen on their surfaces. Similar studies were performed by using AKR anti-C3H serum that contained anti-Thy 1.2 antibodies and autothymocytotoxic antibodies (reactive with AKR thymocytes). Appropriate titers of both the Thy 1.2 and the autothymocytotoxic antibodies also had greater cytolytic activity against 5 min Con A-pulsed or PNA (+) thymocytes compared with 48 hr Con A-stimulated or PNA (-) thymocytes, respectively. Thus, the cytolytic activity observed in the AKR anti-C3H serum was analogous to that observed with NTA. These results suggest that appropriate titers of Thy 1 antisera may preferentially kill subpopulations of T lymphocytes in a manner similar to NTA.