EFFECTORS IN THE ALLOGRAFT RESPONSE

同种异体移植反应的体外模型表明， IL-2诱导的T辅助（TH）细胞增殖和IL-2/IL-4诱导的T辅助（TH）细胞增殖 细胞毒性T细胞CTL的成熟）。第一类海绵矩阵模型 加上II类主要组织相容性复合物（MHC）移植排斥反应， 体内证实了TH细胞的存在和CTL从前-CTL成熟， 移植部位，但支持传统范式的其他证据是 无托叶生物测定显示辅助细胞细胞因子（IL-1、TNF α）的证据 M-CSF）和TH 2型（TH 2）产生IL-6，但TH细胞增殖 不存在，并且找不到TH 1细胞因子（IL-2、干扰素γ）。 此外，TH 2产物IL-4通过生物测定不存在。为了测试 假设体内模型中不存在TH 1活性， 一些TH 2功能下调，我们计划进一步分析 同种异体移植物的关键TH 1（IL-2，IFNG）和TH 2（IL-4，IL-5）细胞因子， 生物测定、酶免疫测定和海绵细胞中的信使RNA。证据 对于体内TH 2与TH 1亚型的实际选择，将通过以下方法来寻求： 在允许的条件下，对海绵细胞进行有限稀释分析 每种亚型都要克隆。TH 2细胞因子在CTL中的作用 利用来自海绵同种异体移植物的前CTL来确定成熟 在抗原特异性CTL成熟的测定中。 因为海绵同种异体移植物在急性排斥反应的情况下， 炎症反应计划，以分析几个选定的影响， 该反应的组分（前列腺素E2，一氧化氮，精氨酸， 肿瘤坏死因子α和转化生长因子β）对 TH 1和TH 2亚群的细胞增殖和细胞因子产生， 以及前CTL成熟为特异性CTL。我们假设 某些急性炎症因子组合将下调细胞内 增殖和促进选择性细胞因子的产生，同时允许 体内CTL成熟。大量关于 同种异体移植物的体内事件和体外模型之间的差异 应导致拒绝。

In vitro models of allograft reactions suggest central roles for IL-2-induced proliferation of T helper (TH) cells and IL-2/IL-4-induced maturation of cytotoxic T cells CTL). The sponge matrix model of class I plus class II major histocompatibility complex (MHC) allograft rejection in vivo confirms the presence of TH cells and CTL maturation from pre-CTL at the graft site, but other evidence to support the conventional paradigm is absent. Bioassays show evidence of accessory cell cytokines (IL-1,TNFa M-CSF) and the TH type 2 (TH2) product IL-6, but proliferation of TH cells is absent, and TH1 cytokines (IL-2, interferon gamma) cannot be found. Furthermore, the TH2 product IL-4 is absent by bioassay. In order to test the hypothesis that TH1 activity is absent in the in vivo model and that some TH2 functions are downregulated, we plan to further analyze the allograft for critical TH1 (IL-2, IFNG) and TH2 (IL-4, IL-5) cytokines by bioassay, enzyme-immune assay, and messenger RNA in sponge cells. Evidence for actual selection of TH2 vs TH1 subtypes in vivo will be sought by limiting dilution analysis of sponge cells under conditions which permit each of the subtypes to be cloned. The role of TH2 cytokines in CTL maturation will be determined utilizing pre-CTL from the sponge allograft in an assay of antigen-specific CTL maturation. Because the sponge allograft is rejected in the context of an acute inflammatory response plan to analyze the effects of several selected components of that response (prostaglandin E2, nitric oxide, arginine, tumor necrosis factor alpha, and transforming growth factor beta) on the cellular proliferation and cytokine production by TH1 and TH2 subsets, as well as on the maturation of pre-CTL to specific CTL. We hypothesize that some combination of acute inflammatory factors will downregulate cellular proliferation and foster selective cytokine production, while permitting CTL maturation in vivo. Considerable information concerning the discrepancies between in vivo events and in vitro models of allograft rejection should result.