Aqueous antigens induce in vivo tolerance selectively in IL-2- and IFN-gamma-producing (Th1) cells.
As a model for understanding in vivo immune responses, we have exposed mice to aqueous haptenated-protein Ag, and examined immune responses to subsequent immunization with Ag in adjuvant. Pretreating mice with soluble, TNP-conjugated Ag induces selective nonresponsiveness to Ag for both humoral and cell-mediated immune functions. Specific T cell proliferation in response to Ag is inhibited, and Ag-induced secretion of the lymphokines IL-2 and IFN-gamma, but not IL-4, is reduced. B cell responses after pretreatment are also affected. Although levels of TNP-specific IgG1 and IgE are similar in treated and untreated mice, soluble Ag pretreatment diminishes production of TNP-specific IgG2a and IgG2b. This is due to lack of T cell help and is not caused by tolerance in the B cell compartment. These results indicate that pretreatment of mice with aqueous Ag induces selective unresponsiveness in Th1-like Th cells, which secrete IL-2 and IFN-gamma, but not in Th2-like Th cells, which secrete IL-4.
Burstein
H J
HJ
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
Shea
C M
CM
Abbas
A K
AK
D000818:Animals; D000941:Antigens / Q000737:chemistry*; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000276:immunology; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology; D014867:Water
D000941:Antigens; D006241:Haptens; D007376:Interleukin-2; D014301:Trinitrobenzenes; D014867:Water; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D006433:Hemocyanins