ROLE OF MHC ANTIGEN INDUCTION IN GRAFT REJECTION

我们建议研究的长远目标，是 理解拒绝和容忍的机制 移植组织 这些知识应该适用于 人类同种异体移植物的维持，生殖问题 免疫学，对人类肿瘤免疫的诱导性，以及 自身免疫性疾病的治疗 该项目的具体目标是确定主要 组织相容性复合物（MHC）抗原在同种异体移植物中表达 拒绝和宽容。 这些研究将跟进 初步实验表明， MHC诱导和移植物排斥反应以及抑制该反应的方法 甲状腺移植物培养后的表达及其诱导 高压氧 我们将首先确定体外 诱导和抑制类表达所需的条件 新鲜和氧培养的内分泌细胞中MHC Ⅰ类和Ⅱ类抗原的表达 组织;其次，我们将确定MHC的影响 表达对培养的同种异体移植物的命运;第三，我们将 研究免疫耐受对MHC抗原表达的影响。 为了实现这些目标，我们将使用小鼠甲状腺， 胰岛将在不同的条件下培养， 条件 MHC抗原在组织上的表达将是 通过免疫组织学技术研究。 一些纸巾 将被移植到同系或 同种异体受体。 第一个目标将通过 实验将（a）确定其他因素或条件 高压氧可以抑制MHC的表达， 诱导，和（B）确定所需的体外条件 在培养后丢失后恢复MHC诱导型， 高压氧 第二个目标将通过测定氧培养 内分泌同种异体移植物（a）如果淋巴细胞浸润到轻微 抗原可以诱导MHC抗原的表达，（B）如果 氧后MHC抗原表达和诱导的减少 治疗可以部分解释移植物的接受，和（c）如果 实质细胞上allo-MHC抗原的高表达 可能足以引起移植排斥反应 如果MHC 诱导是必要的，但不足以诱导排斥， 在未免疫的受体中培养同种异体移植物，我们将尝试 确定所需的补充因素。 第三个目标将通过使用小鼠的实验来实现， 对培养的同种异体移植物产生了耐受性。 为此目的 我们将（a）确定公差是否影响表达， 诱导移植物上的MHC抗原，和（B）尝试 确定是否存在血清或细胞因子， 可以改变MHC抗原诱导的小鼠。

The long-term objective of our proposed study is to better understand the mechanisms of rejection and tolerance of transplanted tissues. This knowledge should be applicable to the maintenance of human allografts, problems in reproductive immunology, the inducibility of immunity to human tumors, and the treatment of autoimmune diseases. The specific aim of this project is to determine the role of major histocompatibility complex (MHC) antigen expression in allograft rejection and tolerance. These studies will follow up on preliminary experiments that demonstrate a relationship between MHC Induction and graft rejection and an inhibition of that expression and its inducibility following culture of thyroid grafts in hyperbaric oxygen. We will first determine the in vitro conditions required to induce and suppress the expression of class I and class II MHC antigens in fresh and oxygen cultured endocrine tissues; secondly, we will determine the influence of MHC expression on the fate of cultured allografts; and thirdly, we will study the effect of tolerance on the expression of MHC antigens. In order to accomplish these goals we will use mouse thyroids and pancreatic islets which will be cultured under different conditions. The expression of MHC antigens on the tissues will be studied by immunohistological techniques. Some of the tissues will be grafted under the kidney capsule of syngeneic or allogeneic recipients. The first goal will be accomplished by experiments that will (a) determine factors or conditions other than hyperbaric oxygen that can inhibit MHC expression and inducibility, and (b) determine the in vitro conditions required to restore MHC inducibility after its loss following culture in hyperbaric oxygen. The second goal will be studied by determining in oxygen cultured endocrine allografts (a) if the lymphocytic infiltration to minor antigens can induce expression of MHC antigens, (b) if the reduction of MHC antigen expression and inducibility after oxygen treatment can partially explain graft acceptance, and (c) if the hyperexpression of allo-MHC antigens on the parenchymal cells can be enough stimulus to induce graft rejection. If MHC induction is necessary but not sufficient to induce rejection of cultured allografts in unimmunized recipients, we will try to determine the complementary factors that are required. The third goal will be approached by experiments using mice that have developed tolerance to cultured allografts. For this purpose we will (a) determine if tolerance affects the expression and inducibility of MHC antigens on the graft, and (b) attempt to determine if serum or cellular factor(s) are present in tolerant mice that can alter MHC antigen induction.