EFFECTORS IN THE ALLOGRAFT RESPONSE

同种异体移植反应的体外模型表明 IL-2诱导T辅助细胞(TH)增殖及IL-2/IL-4诱导 细胞毒性T细胞成熟(CTL)。第I类海绵矩阵模型 外加II类主要组织相容性复合体(MHC)同种异体移植排斥反应 Vivo证实存在TH细胞和CTL成熟前CTL 但支持传统范式的其他证据是 缺席。生物检测显示辅助细胞细胞因子(IL-1，TNFa 和TH2型(TH2)产物IL-6，但TH细胞的增殖 不存在，也找不到TH1细胞因子(IL-2、干扰素γ)。 此外，通过生物测定，TH2产物IL-4是缺失的。为了测试 体内模型中没有TH1活性的假设，以及 一些TH2功能被下调，我们计划进一步分析 同种异体移植治疗Th1(IL-2，IFNG)和Th2(IL-4，IL-5)细胞因子 海绵细胞的生物测定、酶免疫测定和信使核糖核酸。证据 对于体内TH2和TH1亚型的实际选择，将通过以下方式寻找 海绵细胞在允许条件下的极限稀释分析 要克隆的每个亚型。TH2类细胞因子在CTL中的作用 使用来自同种异体海绵移植物的前CTL来确定成熟度 在抗原特异性CTL成熟试验中。 因为同种异体海绵移植在急性移植的情况下被排斥 炎症反应预案分析选择了几种效果 这种反应的成分(前列腺素E_2、一氧化氮、精氨酸、 肿瘤坏死因子α和转化生长因子β)。 TH1和TH2亚群的细胞增殖和细胞因子的产生 以及前CTL对特异性CTL的成熟。我们假设 急性炎症因子的某些组合将下调细胞 增殖和促进选择性细胞因子的产生，同时允许 CTL在体内成熟。提供了大量关于 同种异体肾移植体内事件与体外模型的差异 应该会导致拒绝。

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.