In vivo induction of tolerance in murine CD4+ cell subsets.
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.
Romball
C G
CG
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Weigle
W O
WO
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000096:biosynthesis; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008808:Mice, Inbred CBA; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D005719:gamma-Globulins / Q000276:immunology
D015704:CD4 Antigens; D008222:Lymphokines; D005719:gamma-Globulins; D015847:Interleukin-4; D017493:Leukocyte Common Antigens