STUDIES OF THE AUTOLOGOUS MIXED LYMPHOCYTE REACTION

在这个项目中，我们正在研究人类T细胞的免疫调节潜能。 由自身MHC抗原激活的细胞存在于B细胞或 巨噬细胞(自身反应性T细胞)。在之前的研究中，我们建立了 在IL-2强化培养中维持的自身反应性T细胞克隆 通过周期性地用自体非T细胞刺激。其中一个克隆人， 被称为MTC-4的，被发现具有双重免疫调节潜力，提供 帮助静息B细胞和抑制商陆-有丝分裂原 (PWM)激活的B细胞。在目前的研究中，我们发现MTC-4助手 功能包括由MTC-4细胞识别II类MHC抗原 通过其与T3相关的T细胞受体。此外，我们还证明了帮手 功能是由一种BCGF样因子介导的，这种因子不同于IL-2和 它既作用于静息(小)B细胞，也作用于激活(大)B细胞。也是 目前的研究表明，MTC-4的T细胞抑制功能是 MTC-4细胞与非T细胞(B细胞+ 单核细胞)，与脉宽调制预孵育4小时，但不与 非T细胞与脉宽调制预孵育24小时；这意味着 抑制功能的诱导依赖于瞬时表达的 MHC相关的表面分子。此外，我们还展示了前处理 含有神经氨酸酶的非T细胞导致非T细胞 MTC-4抑制因子功能。这表明，糖基化状态 非T细胞表面抗原决定非T细胞是诱导辅助还是 来自自身反应性T细胞群体的抑制功能。最后，我们 表明MTC-4的T细胞抑制功能是MHC特异性的 效应期，因为只有MHC匹配的细胞才能被抑制。 这表明在效应器中MHC识别是必要的 细胞与靶细胞的相互作用。总之，这些研究证明 可以诱导自身反应性T细胞提供帮助或抑制 这取决于B细胞刺激的类型。这种双功能赋予了 具有重要动态平衡功能的自体反应细胞。

In this project we are studying the immunoregulatory potential of human T cells which are activated by self-MHC antigens present on B cells or macrophages (autoreactive T cells). In previous studies we established autoreactive T cell clones which are maintained in IL-2 enriched cultures by periodic stimulation with autologous non-T cells. One of these clones, termed MTC-4, was found to have dual immunoregulatory potential, providing help for resting B cells and suppression for pokeweed-mitogen (PWM)-activated B cells. In current studies we showed that MTC-4 helper function involves recognition of class II MHC antigens by the MTC-4 cells via its T3-associated T cell receptor. Further, we showed that the helper function is mediated by a BCGF-like factor which is distinct from IL-2 and which acts on both resting (small) and activated (large) B cells. Also incurrent studies we showed that MTC-4 T cell suppressor function is elicited when MTC-4 cells are co-cultured with non-T cells (B cells plus monocytes) that are pre-incubated with PWM for four hours, but not with non-T cells pre-incubated with PWM for 24 hours; this implies that induction of suppressor function depends on a transiently expressed MHC-associated surface molecule. In addition, we showed that pre-treatment of non-T cells with neuraminidase leads to non-T cells which do induce MTC-4 suppressor function. This suggests that the glycosylation status of non-T cells surface antigen determines whether non-T cells elicit helper or suppressor function from the autoreactive T cell population. Finally, we showed that the MTC-4 T cell suppressor function is MHC-specific in the effector phase in that only MHC matched cells are able to be suppressed. This indicates that MHC recognition is necessary in the effector cell-target cell interaction. In all, these studies establish that autoreactive T cells can be induced to provide either help or suppression depending on the type of B cell stimulus. This bifunctionality endows autoreactive cells with the potential for important homeostatic function.