SUPPRESSOR FACTOR INVOLVED IN ALLOGRAFT UNRESPONSIVENESS

在我们的初步研究中，我们已经建立了基本的杂交 获得产生同种异体抗原抑制性T细胞杂交瘤的技术 特异性和非特异性抑制因子。 本提案的目标是：（1）进一步建立 抗原特异性和非特异性抑制性T细胞杂交瘤细胞系 体细胞杂交技术和抑制性T细胞获得自 小鼠对同种异体皮肤移植物无反应，2）测定体外 混合淋巴细胞对杂交瘤源性抑制因子的作用 培养和细胞介导的细胞毒性测定，3）表征 这些抑制因子的性质通过免疫化学和物理化学 分析，以及4）评估这些抑制因子的能力， 延长同种异体皮肤移植物在体内的存活。 我们相信从拟议的实验中获得的信息， 当与我们以前的结果相结合时，应该可以深入了解 同种异体抗原的T细胞受体的性质及其机制 用于调节同种异体移植物中的细胞-细胞相互作用 反应迟钝 也希望这样的杂交瘤细胞系将服务于 作为生物活性抑制因子的恒定来源， 用作诱导的生物免疫抑制剂，或 维持同种异体移植物无反应性。

In our preliminary studies, we have established the basic hybridization technique to obtain suppressor T cell hybridomas which produce alloantigen specific and nonspecific suppressor factors. The objectives of the current proposal are 1) to further establish antigenspecific andnonspecific suppressor T cell hybridoma lines using somatic cell hybridization techniques and suppressor T cells obtained from mice unresponsive to skin allografts, 2) to determine the in vitro functions of the hybridoma-derived suppressor factors by mixed lymphocyte cultures and cell-mediated cytotoxicity assays, 3) to characterize the nature of these suppressor factors by immunochemical and physico-chemical analyses, and 4) to assess the capacity of these suppressor factors to prolong skin allograft survival in vivo. We believe that the information obtained from the proposed experiments, when coupled with our previous results, should provide insight into the nature of T cell receptors for alloantigens and the mechanisms responsible for the regulation of cell-cell interactions in allograft unresponsiveness. It is also hoped that such hybridoma lines would serve as a constant source of biologically active suppressor factors which could be used as a biological immunosuppressive reagent for the induction or maintenance of allograft unresponsiveness.