Bell E B, Shand F L, Gradwell S
Eur J Immunol. 1977 Jun;7(6):406-12. doi: 10.1002/eji.1830070615.
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.
使用人血清白蛋白（HSA）耐受模型，在未繁殖的大鼠中研究了免疫原维持或延长无反应状态的能力。在通过耐受原（可溶性HSA）诱导高剂量或低剂量耐受的两周内最初用免疫原攻击的大鼠，即使在一年半后仍反应低下，并且在某些情况下，在随后的攻击后反应性降低。免疫原对耐受逃逸的抑制作用得到了正式证明：与未攻击组相比，在第一次攻击6个月后接受第二次免疫原攻击的耐受大鼠合成的抗体较少；每次攻击后，这种抗体的亲和力逐渐下降，这表明高亲和力B细胞逐渐丢失。此外，免疫原维持的耐受大鼠（a）在过继转移时其胸导管淋巴细胞中具有可证明的辅助性T细胞活性，（b）在接受外周T细胞后抗体合成没有显著增加，并且（c）没有提供抑制细胞起作用的证据。结果表明，耐受原诱导耐受和免疫原维持耐受的机制根本不同。
