A Cellular Basis for Genetically Controlled Immunologic Unresponsiveness in Mice: Tolerance Induction in T-Cells

H-2(q) mice (DBA/1) do not make an antibody response to a synthetic aminoacid polymer, (Glu, Ala,Tyr(10)), after an immunizing regimen that produces a good antibody response in mouse strains with other H-2 alleles. Their thymocytes, however, show evidence of recognizing this antigen since they synthesize DNA when they meet the antigen in the spleen. This recognition event does not lead to memory production, as it does in genetic responders, since the thymocytes fail to respond to a second immunization with (Glu,Ala,Tyr(10)). Nonresponder mice do make antibody to (Glu,Ala,Tyr(10)) when they are immunized with it complexed to an immunogenic carrier, but previous treatment with free polymer can temporarily abolish this response. Thus, we suggest that the basis for the unresponsiveness of these mice is that their T-cells (thymus-processed lymphocytes) have an inordinate propensity to become (or to induce other cells to become) immunologically tolerant.