EFFECTORS IN THE ALLOGRAFT RESPONSE

这项赠款提案的目的是确定在什么条件下 迟发性超敏反应(DTH)在排斥反应中起作用 同种异体移植物。定义敏感者能力的三个标准 淋巴细胞与其特定的同种异体抗原接触以诱导迟发型变态反应 假设：(1)转移延迟脚垫肿胀的能力 同基因宿主，(2)招募循环放射性标记的能力 淋巴细胞，增加局部血流量，改变血管通透性， 以及(3)诱导幼稚巨噬细胞改变功能或 在体外损伤组织。迟发型变态反应各组分的检测 反应已经建立起来了。仔细描述了亚种群 同种异体海绵基质细胞跨组织相容性移植 屏障(1类、2类、1类和2类组合、少量抗原性 基因座)将被检测其能力是否符合潜伏期标准。只有一个 将使用单一受体品系的小鼠(B10.AQR)，以便 细胞群体之间的比较可以标准化为所有的基因 差距。同种异体抗原致敏的海绵克隆T细胞 具有良好辅助或细胞毒性特性的同种异体基质移植物 将他们的潜伏期能力与移植物的亚群进行比较。 将特别关注具有辅助功能的克隆 对第二类同种异体抗原有反应。我们希望能够关联到 锥形T细胞群诱发各种迟发型超敏反应的能力 由于其抗原性、表面标志和功能表型， 以及在体外分泌淋巴因子的能力。我们希望 阐明移植物排斥反应中组织破坏的机制 完全没有细胞毒性T细胞，就像在 对移植物的排斥反应仅在2类基因座有差异。

The aim of this grant proposal is to determine under what conditions delayed type hypersensitivity (DTH) reactions play a role in the rejection of allografts. Three criteria which define the capacity of a sensitized lymphocyte in contact with its specific alloantigen to elicit a DTH have been postulated: (1) the capacity to transfer delayed footpad swelling in a syngeneic host, (2) the capacity to recruit circulating radio-labelled lymphocytes, increase regional blood flow and alter vascular permeability, and (3) the capacity to induce naive macrophages to alter function or injure tissue in vitro. Assays for each of these components of DTH reactions have been established. Carefully characterized subpopulations of cells from sponge matrix allografts across defined histocompatibility barriers (Class 1, Class 2, combinations of Class 1 and 2, minor antigenic loci) will be assayed for their capacity to satisfy DTH criteria. Only a single recipient strain of mouse (B10.AQR) will be used so that the comparisons between cell populations can be standardized for all genetic disparities. Alloantigen sensitizied cloned T cells isolated frm sponge matrix allografts with well characterized helper or cytotoxic properties will be compared in their DTH ability with subpopulations from the graft. Particular attention will be focused on clones with helper function responding to class 2 alloantigens. We expect to be able to correlate capacity of a coned T cell population to elicit the various DTH phenomena wih its antigenic specificity, its surface marker and functional phenotype, and with its capacity to secrete lymphokines in vitro. We hope to elucidate the mechanisms of tissue destruction during graft rejection in the total absence of cytotoxic T cells such as that seen during the rejection of grafts disparate only at the class 2 loci.