MURINE T LYMPHOCYTE SUBSETS AND ALLOGRAFT REJECTION

鼠 T 淋巴细胞亚群和同种异体移植排斥

• 批准号: 3810524
• 负责人: FRANK W FITCH
• 金额: --
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3810524
• 关键词: CD4 molecule; CD8 molecule; MHC class I antigen; MHC class II antigen; T cell receptor; athymic mouse; autologous transplantation; cell type; clone cells; cytotoxic T lymphocyte; flow cytometry; hamsters; helper T lymphocyte; histocompatibility; homologous transplantation; immunoregulation; immunosuppression; immunotherapy; interferons; interleukin 1; interleukin 2; interleukin 4; laboratory mouse; laboratory rat; leukocyte activation /transformation; lymphokines; monoclonal antibody; suppressor T lymphocyte; surface antigens; tissue /cell culture

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.

T淋巴细胞在细胞和体液免疫应答中起核心作用， 它们是同种异体移植排斥反应的原因一些T的表达 细胞表面结构与MHC抗原的种类相关， 限制了它们的反应：通常，CD 8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CD 4， 其受II类MHC抗原限制或与II类MHC抗原反应。T细胞 表达CD 4的细胞已经在以下阵列的基础上进一步细分： 分泌性淋巴因子：T（H）1细胞分泌IL-2和IFN-γ，但不分泌IL-4 或IL-5，而T（H）2细胞分泌IL-4和IL-5，但不分泌IL-2或IFN-γ。 然而，一些CD 4+细胞不属于这些类别。大多数CD 8 + T细胞依赖于由CD 4+细胞提供的生长因子，有些是 帮助者独立虽然T细胞执行直接效应功能 例如细胞溶解和通过分泌介导调节功能 淋巴因子，它们引起同种异体移植排斥反应的机制是 特征不佳。在所选基因中不同的同类小鼠品系 MHC复合体的区域提供了有用的模型系统用于研究 不同T细胞亚群在移植排斥反应中的作用。均为CD 4 + CD 8+细胞似乎参与了小鼠同种异体移植物的排斥反应 其仅在H-2K（B）和I-A（B）上不同，而似乎仅CD 8+细胞是 H-2L（d）同种异体移植物排斥反应所需的时间。拟议的研究将 确定参与同种异体移植排斥反应的T细胞种类， 在MHC复合体的特定、确定区域与宿主不同， 通过描述这些T细胞引起移植的机制， 排斥反应我们将：1）衍生与H-2L（d）I类反应的克隆T细胞 MHC抗原和确定产生的淋巴因子的阵列和钟 表面分子表示; 2）表征变量的基础 在一些与H-2L反应的CD 8 + CTL中表达细胞溶解活性（d） I类MHC抗原; 3）确定是否存在CD 8+鼠MHC抗原的亚群， 对应于T（H）1和T（h）2的T细胞以及CD 4 + T细胞的其他亚群 鼠T细胞;和4）开发抑制同种异体移植物的策略 排斥反应，包括使用与淋巴因子反应的单克隆抗体 或细胞表面结构的特定T细胞亚群。