In Vivo Induction of Tolerance in Murine CD4

Summary The induction of tolerance in mice to preparations of deaggregated human gamma globulin (DHGG) results in in vitro antigen-specific unresponsiveness in CD4 + T cells as well as in both the T helper 1 (Thl) and Th2-1ike subpopulations. Whereas both CD45RB hi and CD45RB l~ cells from lymph nodes of HGG/complete Freund's adjuvant-immunized mice (control) proliferated in vitro to HGG, both subpopulations from mice previously tolerized with DHGG failed to respond. Furthermore, CD4 + T cells from control, but not from DHGG-injected mice, secreted high levels of interleukin 2 (IL-2) after in vitro stimulation with HGG. Although significant levels of IL-4 in supernatants of control CD4 + cells stimulated with HGG were detected in some, but not all, experiments, significant levels of IL-4 were never detected in supernatants of HGGstimulated tolerant CD4 + cells. The demonstration that serum IgG1 anti-HGG is preferentially produced in a few tolerant mice that exhibit a leaky tolerant state suggests that tolerance induction may be more dif~cult to induce in IL-4- than in IL-2-producing cells.