Cellular events in protein-tolerant inbred rats. IV. The mechanism of immunogen-maintained tolerance.
The ability of immunogens to maintain or extend a state of unresponsiveness was investigated in unbred rats using a human serum albumin (HSA) model of tolerance. Rats initially challenged with immunogen within two weeks of high or low dose tolerance induction by tolerogen (soluble HSA) remained hyporesponsive even a year and a half later and in some cases became less responsive following a subsequent challenge. An inhibitory effect of immunogen on escape from tolerance was formally demonstrated: in comparison with an unchallenged group, tolerant rats which received a second immunogen challenge 6 months after the first, synthesized less antibody; this antibody underwent a gradual decline in affinity after each challenge which suggested that higher avidity B cells were progressively lost. In addition, immunogen-maintained tolerant rats (a) had demonstrable helper T cell activity among their thoracic duct lymphocytes on adoptive transfer, (b) did not produce a significant increase in antibody synthesis after receiving peripheral T cells and (c) provided no evidence that suppressor cells were playing a role. The results suggested that the mechanisms of tolerance induction by tolerogen and tolerance maintenance by immunogen are fundamentally different.
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D000941:Antigens / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology*; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000941:Antigens; D012709:Serum Albumin