MURINE T LYMPHOCYTE SUBSETS AND ALLOGRAFT REJECTION

T淋巴细胞在细胞和体液免疫反应中发挥核心作用， 他们要对同种异体移植的排斥反应负责。关于某些T的表达 细胞表面结构与MHC抗原的类别相关 限制他们的反应：通常，CD8存在于T细胞上， 受I类MHC抗原限制或与I类MHC抗原反应，而在T细胞上发现CD4 它们受第二类MHC抗原的限制或与之反应。T细胞 其表示的CD4已经根据数组被进一步细分 分泌性淋巴因子：T(H)1细胞分泌IL-2和干扰素-γ，但不分泌IL-4 T(H)2细胞分泌IL-4和IL-5，但不分泌IL-2或干扰素-γ。 然而，一些CD4细胞并不属于这些类别。而大多数CD8 T细胞依赖于由CD4细胞提供的生长因子，有些是 独立于帮助者。尽管T细胞执行直接效应功能 例如细胞溶解和通过分泌 淋巴因子，它们引起同种异体移植排斥的机制是 特征不佳的。选择的不同的同源小鼠品系 MHC复合体的区域提供了有用的模型系统来研究 不同T细胞亚群在同种异体排斥反应中的作用两者都是CD+4 CD8细胞似乎参与了小鼠同种异体移植的排斥反应 它们只在H-2K(B)和I-A(B)上不同，而只有CD8细胞似乎是 H-2L(D)同种异体移植排斥所需。拟议的研究将 定义参与同种异体移植排斥反应的T细胞的种类 在MHC复合体的特定、定义的区域与宿主不同 通过描述这些T细胞引起移植物的机制 拒绝。我们将：1)获得与H-2L(D)I类反应的克隆T细胞 并测定MHC抗原和淋巴因子阵列的产生及铃声 所表达的表面分子；2)表征变量的基础 某些CD8CTL与H-2L(D)反应后细胞杀伤活性的表达 I类MHC抗原；3)确定是否存在CD8小鼠亚群 T细胞与T(H)1、T(H)2及其他亚群的CD4 小鼠T细胞；以及4)开发抑制同种异体移植的策略 排斥反应，包括使用与淋巴因子反应的单抗 或特定T细胞亚群上的细胞表面结构。

T lymphocytes play a central role in cellular and humoral immune responses, and they are responsible for rejection of allografts. Expression of some T cell surface structures correlates with the class of MHC antigen which restricts their responses: generally, CD8 is found on T cells which are restricted by or reactive with class I MHC antigens while CD4 is found on T which are restricted by or reactive with class II MHC antigens. T cells which express CD4 have been subdivided further on the basis of the array of secreted lymphokines: T(H)1 cells secrete IL-2 and IFN-gamma but not IL-4 or IL-5 while T(H)2 cells secrete IL-4 and IL-5 but not IL-2 or IFN-gamma. However, some CD4+ cells do not fit into these categories. While most CD8+ T cells are dependent on growth factors supplied by CD4+ cells, some are helper-independent. Although T cells carry out direct effector functions such as cytolysis and mediate regulatory functions via secreted lymphokines, the mechanisms by which they cause allograft rejection are poorly characterized. Congenic mouse strains which differ in selected regions of the MHC complex provide useful model systems for studying the functions of the different T cell subsets in allograft rejection. Both CD4+ and CD8+ cells appear to be involved in the rejection of murine allografts which differ only in H-2K(b) and I-A(b), while only CD8+ cells appear to be required for rejection of H-2L(d) allografts. The proposed studies will define the kinds of T cells involved in rejection of allografts which differ from the host in specific, defined regions of the MHC complex and with characterizing the mechanisms by which these T cells cause graft rejection. We will: 1) derive cloned T cells reactive with H-2L(d) class I MHC antigen and determine the array of lymphokines produced and the bell surface molecules expressed; 2) characterize the basis for the variable expression of cytolytic activity in some CD8+ CTL which react with H-2L(d) class I MHC antigens; 3) determine whether there are subsets of CD8+ murine T cells corresponding to the T(H)1 and T(h)2 and other subsets of CD4+ murine T cells; and 4) develop strategies for suppressing allograft rejection including use of monoclonal antibodies reactive with lymphokines or cell surface structures on the particular T cells subsets.