Antigen recognition by T cells. II. Intravenous administration of native or denatured ovalbumin results in tolerance to both forms of the antigen.
In the accompanying report, suppressor T cells were demonstrated that did not recognize cross-reactivity between native and denatured ovalbumin (N-OVA and D-OVA). Here we show that the T cell tolerance induced by i.v. injections of antigen does detect cross-reactivity between N-OVA and D-OVA. Mice that had been immunized with either N-OVA or D-OVA in adjuvant could be rendered profoundly unresponsive if either N-OVA or D-OVA, but not an unrelated protein, were injected i.v. Cross-tolerance was observed in assays of antigen-induced T cell proliferation and helper T cell activity. Tolerance was distinguished from suppressor T cell activity by three criteria: 1) specificity for N-OVA and D-OVA, 2) sensitivity to abrogation by cyclophosphamide, 3) duration of effectiveness. These results confirm observations made by others that suggest that tolerance is mediated by an additional mechanism(s) other than suppressor T cells. Based on a hypothesis that cross-reactivity between native and denatured antigen is related to macrophage processing of antigen, these data also suggest a critical role for processed antigen in the induction of tolerance when antigen is administered i.v.
D000818:Animals; D000941:Antigens; D002455:Cell Division; D003429:Cross Reactions; D003520:Cyclophosphamide / Q000494:pharmacology; D000939:Epitopes; D007108:Immune Tolerance; D007275:Injections, Intravenous; D008264:Macrophages / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000941:Antigens; D000939:Epitopes; D003520:Cyclophosphamide; D010047:Ovalbumin