Green D R, Chue B, Gershon R K
Department of Pathology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut.
J Mol Cell Immunol. 1983;1(1):19-30.
Contrasuppression is an immunoregulatory T cell activity that augments immune responses by interfering with suppressor T cell function. Since contrasuppression appears to play a role in autoimmunity, hyperimmunity, and recovery from induced general unresponsiveness (such as appears following burn trauma), an understanding of how contrasuppression is controlled may have profound implications for understanding immune regulation as well as for manipulating immune responses. Further, since inhibition of contrasuppressor function would appear as suppression, identifying cells able to perform this function would describe at least two modes of suppression in immune regulation, and allow a synthesis of regulatory T cell circuits not previously possible. In the studies described, we have sought to identify distinct lymphocyte subpopulation(s) having the specialized activity of regulating the cells of the contrasuppressor circuit. Two experimental systems have been previously examined. In the first, cells regulating the appearance of contrasuppressor effector T cells generated in cultures of neonatal spleen cells have been characterized. In the second, cells producing a contrasuppressor inducer factor derived from antigen-stimulated Ly-2 T cells have been studied, as well as their cellular targets. Regulation of contrasuppressor T cell activation in both systems by various cell populations was characterized by means of antisera against cell surface differentiation antigens. Our studies demonstrate that an I-J+, Ly-1,2 cell whose activity is not apparent before 1-2 weeks postbirth appears in adult T cell populations and regulates the generation of contrasuppressor cells in neonatal cell cultures. This adult cell can be removed with a low concentration of a monoclonal anti-T cell reagent. Removal of these T cells from adult populations allows the generation of an adult contrasuppressor effector cell indistinguishable from the one found in neonatal spleen by means of the spleen cell culture system. Adult antigen-primed Ly-2 T cells, used for the production of suppressor factor, contain a cell sensitive to the monoclonal antibody that normally prevents the dominance of contrasuppression over suppression. We refer to this cell as a "level 2" suppressor because after its removal contrasuppression is found, and after this contrasuppression is eliminated by selective antiserum treatment suppression is observed. This indicates that a "level 1" suppressor exists, but effector factors mediating this suppression are significantly more susceptible to contrasuppression than are those of "level 2" suppressor cells. Our findings demonstrate two types of suppressor cell circuits
抗抑制是一种免疫调节性T细胞活性，它通过干扰抑制性T细胞功能来增强免疫反应。由于抗抑制似乎在自身免疫、超敏免疫以及从诱导的全身无反应状态（如烧伤创伤后出现的情况）恢复过程中发挥作用，因此了解抗抑制是如何被控制的，可能对理解免疫调节以及操纵免疫反应具有深远意义。此外，由于抑制抗抑制功能会表现为抑制作用，识别能够执行这种功能的细胞将描述免疫调节中至少两种抑制模式，并允许合成以前不可能的调节性T细胞回路。在所描述的研究中，我们试图识别具有调节抗抑制回路细胞特殊活性的不同淋巴细胞亚群。此前已经研究了两种实验系统。第一种是对调节新生脾细胞培养物中产生的抗抑制效应T细胞出现的细胞进行了表征。第二种是研究了产生源自抗原刺激的Ly-2 T细胞的抗抑制诱导因子的细胞及其细胞靶点。通过针对细胞表面分化抗原的抗血清，对各种细胞群体在这两种系统中对抗抑制性T细胞激活的调节进行了表征。我们的研究表明，一种I-J⁺、Ly-1,2细胞在出生后1至2周前其活性不明显，出现在成年T细胞群体中，并调节新生细胞培养物中抗抑制细胞的产生。这种成年细胞可以用低浓度的单克隆抗T细胞试剂去除。从成年群体中去除这些T细胞后，通过脾细胞培养系统可以产生一种与在新生脾中发现的抗抑制效应细胞无法区分的成年抗抑制效应细胞。用于产生抑制因子的成年抗原致敏Ly-2 T细胞含有一种对单克隆抗体敏感的细胞，该单克隆抗体通常可防止抗抑制作用超过抑制作用。我们将这种细胞称为“2级”抑制细胞，因为去除它后会出现抗抑制作用，而在用选择性抗血清处理消除这种抗抑制作用后会观察到抑制作用。这表明存在“1级”抑制细胞，但介导这种抑制作用的效应因子比“2级”抑制细胞的效应因子更容易受到抗抑制作用的影响。我们的发现证明了两种类型的抑制细胞回路
