Transmission of hapten-specific tolerance to an unrelated carrier.
The principle of linked recognition is well defined in response and suppression. Yet, to our knowledge, it is not explored in the context of tolerance. To investigate, whether the status of tolerance toward a hapten (TNP) can be transferred to a subsequently introduced carrier, animals which were tolerized by a subimmunogenic dose of hapten (TNP) coupled to syngeneic monoclonal anti-TNP IgG, with the rationale of combining the phenomena of low zone tolerance and syngeneic IgG-induced suppression, were challenged with TNP-horse red blood cells (HRBC). Conjugates of high density (40 mM) TNP-syngeneic IgG (TNP40-IgG) were immunogenic and after challenge with TNP-HRBC, animals responded to TNP and to HRBC. Yet, spleen cells (SC) of mice injected with TNP2.5-IgG and challenged with TNP-HRBC were tolerant against TNP as well as the carrier. Limiting dilution (LD) analysis revealed that subimmunogenic doses of TNP coupled to IgG resulted in diminished activation of help, failure to activate contrasuppressor T cells (TCS), and significantly augmented activation of suppressor T cells (TS). On the other hand, after challenge with TNP-HRBC, activation/expansion of carrier-specific helper (TH), suppressor, and contrasuppressor T cells were not affected by previous immunization with subimmunogenic or immunogenic doses of TNP-IgG conjugates, but HRBC-specific TCS could not interact with TNP-specific TS. Hence, to initiate tolerance it was necessary (and sufficient) that an activated and expanded TS population was not counterregulated by TCS. In this situation, an established status of dominance of suppression for the epitope TNP could not be disrupted by an immunogene carrying a multitude of new epitopes; i.e., tolerization by subimmunogenic doses of the individual epitope TNP resulted in unresponsiveness against any immunogen carrying this epitope.
D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D004912:Erythrocytes / Q000276:immunology; D006241:Haptens / Q000276:immunology*; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000276:immunology; D008211:Lymphocyte Cooperation; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology
D000939:Epitopes; D006241:Haptens; D007136:Immunoglobulins; D014301:Trinitrobenzenes