ROLE OF MHC ANTIGEN INDUCTION IN GRAFT REJECTION

我们建议的研究的长远目标是更好地 理解拒绝和容忍的机制 移植的组织。这一知识应该适用于 人类同种异体移植的维护，生殖方面的问题 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。 这个项目的具体目标是确定主要的 组织相容性复合体抗原在同种异体移植物中的表达 拒绝和宽容。这些研究将跟进 初步实验证明了 MHC诱导和移植物排斥反应及其抑制 甲状腺移植物培养后的表达及其诱导性 在高压氧中。我们将首先测定体外培养的 诱导和抑制类的表达所需的条件 新鲜和氧气培养的内分泌中的I和II类MHC抗原 组织；其次，我们将确定MHC的影响 表达培养的同种异体移植物的命运；第三，我们将 研究耐受对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和 胰岛在不同的培养条件下培养 条件。MHC抗原在组织上的表达将是 通过免疫组织学技术进行研究。一些组织 将移植肾包膜下的同基因或 异基因移植受者。第一个目标将通过以下方式实现 将(A)确定其他因素或条件的实验 高压氧可以抑制MHC的表达和 诱导性，以及(B)确定所需的体外条件 MHC在培养后丧失诱导性后恢复 高压氧。 第二个目标将通过在氧气培养中进行测定来研究 同种异体内分泌移植(A)若淋巴细胞浸润至微小 抗原可以诱导MHC抗原的表达，(B)如果 氧疗后MHC抗原表达和诱导性的降低 治疗可以部分解释移植物的接受性，以及(C)如果 异种MHC抗原在实质细胞上的高表达 可以有足够的刺激来诱导移植物排斥反应。如果MHC 诱导是必要的，但不足以诱导排斥 在未免疫的受者中培养的同种异体移植，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进行实验来实现 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)确定容差是否会影响表达式和 移植物上MHC抗原的诱导性，以及(B)试图 确定耐受患者是否存在血清或细胞因子(S) 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.