T-T COLLABORATION IN THE REJECTION OF ISLET ALLOGRAFTS

培养的胰岛簇同种异体移植物在放置于 免疫活性同种异体受体的肾包膜不同于 主要组织相容性复合体（MHC）。 如果发生拒绝， 接受者被注射了来自与受试者同基因的供体的T细胞。 接受者先前已接受移植物的淋巴细胞预处理 供体单倍型。 来自正常、未致敏供体的T细胞不诱导 排斥反应 T细胞的细胞毒性/抑制子亚群的消除 废除拒绝。 这一结果的一个结论是，细胞毒性T 在该动物模型中，淋巴细胞（CTL）是移植物排斥反应所必需的 系统 该项目的目的是确定CTL是否足够， 需要与其他T细胞亚群协作。 待检验的假设是I类MHC特异性CTL 培养的胰岛同种异体移植物的同种抗原需要帮助，最有可能是在 IL-2的形式，来自对I类MHC抗原特异的辅助性T细胞 （I类特异性辅助者）和脱落的移植物同种异体抗原， 移植受体MHC（生理辅助）的背景。 在该提议中，体内分离程序（阴性选择）是 介绍了 在负选择的情况下，所提供的数据表明， 可以通过功能将CTL与I类特异性CTL区分开， 生理助手 所提供的数据也将显示，消除， 通过阴性选择，所有三个子集都废除了 剩余的T细胞诱导排斥反应。 通过适当选择 程序，在文本中详细描述，它将有可能 确定CTL亚群是否单独或与其他T细胞协作 亚群可诱导移植物排斥。 这项研究，它独特地确定了 T细胞亚群的功能和特异性，应提供有用的 关于T细胞介导的免疫调节机制的一般问题的信息 移植排斥反应

Cultured islet cluster allografts were not rejected when placed under the kidney capsule of immunocompetent allogeneic recipients differing from the donor at the major histocompatibility complex (MHC). Rejection occurred if the recipients were injected with T cells from donors syngeneic to the recipient who had been previously primed to lymphoid cells of the graft donor haplotype. T cells from normal, unprimed donors did not induce rejection. Elimination of the cytotoxic/suppressor subset of T cells abrogated rejection. One conclusion of this result is that cytotoxic T lymphocytes (CTL) are necessary for graft rejection in this animal model system. The aim of the project is to determine whether the CTL are sufficient or if collaboration with other T cell subsets is required. The hypothesis to be tested is that CTL specific for the class I MHC alloantigens of the cultured islet allograft require help, most likely in the form of IL-2, from helper T cells specific for class I MHC antigens (class I specific helpers) and shed graft alloantigens represented in the context of the graft recipients MHC (physiologic helper). In this proposal an in vivo separation procedure (negative selection) is described. With negative selection the data presented show that it should be possible to distinguish, by function, CTL from class I specific and physiologic helpers. The data presented also will show that elimination, via negative selection, of all three subsets abolishes the capacity of the remaining T cells to induce rejection. By appropriate selection procedures, described in detail in the text, it will be possible to determine if the CTL subset by itself or in collaboration with other T cell subsets can induce graft rejection. This study, which uniquely identifies T cell subsets by function and specificity, should provide useful information on the general question of the mechanism of T cell mediated graft rejection.