STUDIES OF THE AUTOLOGOUS MIXED LYMPHOCYTE REACTION

本课题针对自体混合体的研究。 淋巴细胞反应(AMLR)，T细胞的增殖反应 大约是由于他们接触了自体B细胞和巨噬细胞。在 本系列研究报告了自身反应性T细胞的建立 细胞克隆及其免疫调节能力的性质 克隆人。在最初的研究中，我们发现自体反应性T细胞在 由提出的抗原(破伤风类毒素)重复刺激的培养 自体非T细胞(在IL-2存在下)。这样的细胞出现在 抗原反应性T细胞，但可以从后者中分离出来，然后 使用有限稀释技术进行扩展。一种自体反应 克隆名为MTC-4，具有辅助细胞的表型(Leu3+，Leu2-)和 与自体细胞共培养时发生增殖，但不 同种异体非T细胞。有趣的是，免疫调节的潜力 MTC-4细胞根据细胞被激活的方式而不同。当MTC-4 在没有抗原的情况下，将细胞与自体非T细胞一起培养 或有丝分裂原，观察多克隆免疫球蛋白的产生。这个帮手 活性受到MHC的限制，因为它只能由自体 非T细胞或MHC匹配的同种异体非T细胞；然而，一旦被激活 通过自体非T细胞，MTC-4细胞也可以帮助异体非T细胞 细胞。相反，当MTC-4细胞与自体非T细胞共同培养时 细胞在商陆有丝分裂原(PWM)存在下，产生免疫球蛋白 被打压了。这种抑制不是由于脉宽调制的直接作用。 MTC-4细胞，因为后者在培养前与PWM预先孵育 对非T细胞无抑制作用。在此基础上 数据表明，自身反应性T细胞具有双重调节能力 这是由激活模式不同地引起的：1)当 受未激活的B细胞上存在的MHC抗原刺激，它们提供 辅助活动；以及2)当受到MHC抗原刺激时 激活的B细胞，它们提供抑制活性。自身反应性细胞 具有这些特性的人独特地适应于保持免疫力 动态平衡。

This project is directed toward the study of the autologous mixed lymphocyte reaction (AMLR), the proliferative response of T cells brought about by their exposure to autologous B cells and macrophages. In the present series of studies we report on the establishment of autoreactive T cell clones and the nature of the immunoregulatory capacity of such clones. In initial studies we found that autoreactive T cells develop in cultures repetitively stimulated by antigen (tetanus toxoid) presented by autologous non-T cells (in the presence of IL-2). Such cells appear along with antigen-reactive T cells, but can be isolated from the latter and then expanded using limiting dilution techniques. One of the autoreactive clones, termed MTC-4, has the phenotype of "helper" cell (Leu3+, Leu2-) and undergoes proliferation when co-cultured with autologous, but not allogeneic non-T cells. Of interest, the immunoregulatory potential of MTC-4 cells varied according to how the cells were activated. When MTC-4 cells were cultured with autologous non-T cells in the absence of antigen or mitogen, polyclonal immunoglobulin production was observed. This helper activity was MHC-restricted in that it was elicited only by autologous non-T cells or MHC matched allogenic non-T cells; however, once activated by autologous non-T cells, MTC-4 cells could also help allogeneic non-T cells. In contrast, when MTC-4 cells were cultured with autologous non-T cells in the presence of pokeweed mitogen (PWM), immunoglobulin production was suppressed. This suppression was not due to a direct effect of PWM on MTC-4 cells, since pre-incubation of the latter with PWM prior to culture with non-T cells did not result in suppression. On the basis of these data, we conclude that autoreactive T cells have dual regulatory capability which is differentially elicited by the mode of activation: 1) when stimulated by MHC antigens present on unactivated B cells, they provide helper activity; and 2) when stimulated by MHC antigens present on activated B cells, they provide suppressor activity. Autoreactive cells with these properties are uniquely adapted to maintain immunologic homeostasis.