Mohler K M, Streilein J W
Department of Microbiology and Immunology, University of Miami Medical School, Florida 33136.
Transplantation. 1989 Apr;47(4):633-40. doi: 10.1097/00007890-198904000-00014.
Since tolerogen-specific helper activity is present in MLR-positive class II MHC tolerant mice, a loss of helper activity is unlikely to be responsible for the maintenance of tolerance in these mice. An alternative hypothesis, that effector cell function is selectively down-regulated, has been examined with lymphocytes from MLR-positive class-II MHC tolerant mice on both the A strain and the B10 background. The results demonstrate that lymphocytes from A-strain-tolerant mice were unable to generate tolerogen-specific effector cells in any of the assays tested (CML with or without exogenous growth factor and DTH following in vivo priming or local adoptive transfer), even though these mice possess tolerogen-responsive T helper cells. In contrast, a majority of MLR-positive tolerant mice on the B10 background generated measurable tolerogen-specific cytotoxic activity in the absence of exogenous growth factor, and all the mice examined generated substantial cytotoxic activity in the presence of exogenous growth factor. However, in a local adoptive transfer reaction, lymphocytes from these mice failed to display DTH. It is concluded that tolerance is maintained by selective impairment of class II specific effector functions and that regulation of DTH rather than CTL activity may be central to maintenance of in vivo tolerance to class II MHC antigens.
由于在MLR阳性的II类MHC耐受小鼠中存在耐受原特异性辅助活性，辅助活性的丧失不太可能是这些小鼠维持耐受的原因。另一种假设，即效应细胞功能被选择性下调，已在A品系和B10背景的MLR阳性II类MHC耐受小鼠的淋巴细胞中进行了研究。结果表明，来自A品系耐受小鼠的淋巴细胞在任何测试的实验中（有或没有外源性生长因子的CML以及体内致敏或局部过继转移后的DTH）都无法产生耐受原特异性效应细胞，尽管这些小鼠拥有耐受原反应性T辅助细胞。相比之下，大多数B10背景的MLR阳性耐受小鼠在没有外源性生长因子的情况下产生了可测量的耐受原特异性细胞毒性活性，并且所有检查的小鼠在有外源性生长因子的情况下都产生了大量的细胞毒性活性。然而，在局部过继转移反应中，来自这些小鼠的淋巴细胞未能表现出DTH。结论是，通过II类特异性效应功能的选择性损伤来维持耐受，并且DTH的调节而非CTL活性可能是维持对II类MHC抗原体内耐受的关键。
