Journal of Experimental Medicine, Vol 178, 1637-1644, Copyright © 1993 by Rockefeller University Press

ARTICLES

In vivo induction of tolerance in murine CD4+ cell subsets

CG Romball and WO Weigle
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.

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 (Th1) and Th2-like subpopulations. Whereas both CD45RB(hi) and CD45RB(lo) 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 HGG-stimulated 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 difficult to induce in IL-4- than in IL- 2-producing cells.
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