PROLIFERATIVE T-CELL ANERGY TO MLS-1A DOES NOT CORRELATE WITH INVIVO TOLERANCE

Intravenous or intraperitoneal priming of Mls-1b mice with cells from Mls-1a donors drastically reduces secondary in vitro proliferative responses to specific stimulation. We show here that: (i) priming leads to blast transformation of essentially all CD4+ T cells bearing V-beta-6 receptors in spleen and lymph nodes, and to their marked clonal expansion; (ii) secondary in vivo (or in vitro) challenges have no effect on the state of activation and numbers of V-beta-6 CD4 T cells, which, however, migrate to the site of antigenic exposure; (iii) priming results in the differentiation of specific V-beta-6 CD4 T cells to effector helper activities, manifested in vivo by marked increases in the numbers of splenic plasma cells, which include terminally differentiated donor Mls-1a B cells; (iv) primed mice show accelerated 'second set' rejection of antigenic cells; and (v) Mls-1b mice, thymectomized as adults before exposure to Mls-1a cells, show immune responses that are equivalent to those of control animals. We conclude that, in this experimental system, proliferative 'anergy' does not correlate with tolerance but with memory, and relates to the determination of class in immune responses.