LIVER TRANSPLANTATION--THE ROLE OF DENDRITIC CELLS

描述：（改编自申请人的摘要）应注意， 小鼠原位肝移植模型导致几乎100 耐受性百分比和不需要 免疫抑制，也导致树突状细胞的转移 系统地在接受者体内。 祖树突细胞是 II类MHC和刺激分子表达缺陷， 同种异体刺激活性，也可以延长同种异体移植物的存活， 某些情况下。这些祖细胞的免疫抑制特性 树突状细胞受细胞因子和基质的控制， 交互.因此，申请人假设， 细胞表面MHC抗原和T细胞共刺激因子的表达 树突状细胞上的分子决定了它们诱导 宽容和免疫。提出了三个具体目标：一。确定 细胞因子和基质蛋白如何改变细胞的表型和功能 肝树突状细胞 二.定义细胞和分子机制 树突状细胞表型和功能的改变改变了T 体外细胞反应。三. 建立体内相关性 树突状细胞共刺激分子表达的改变 扩展了他们的观察，即树突状祖细胞促进了 器官移植存活率。

DESCRIPTION: (Adapted from the applicant's abstract) It is noted that the orthotopic liver transplant model in mice results in virtually 100 percent tolerance and survival of recipients without need for immunosuppression and also results in transfer of dendritic cells systemically within the recipient. Progenitor dendritic cells are deficient in MHC Class II and stimulatory molecule expression and allostimulatory activity and can also prolong allograft survival in certain circumstances. These immunosuppressive properties of progenitor dendritic cells are controlled by both cytokines and by matrix interactions. Therefore the applicant hypothesizes that regulation of the expression of cell surface MHC antigens and T cell costimulatory molecules on dendritic cells determines their potential to induce tolerance and immunity. Three specific aims are proposed: I. Determine how cytokines and matrix proteins alter the phenotype and function of liver dendritic cells. II. Define the cellular and molecular mechanisms by which alterations in dendritic cell phenotype and function alter T cell responses in vitro. III. Establish the in vivo relevance of alterations in dendritic cell expression of co-stimulatory molecules by extending their observation that dendritic progenitors promote the survival of organ allografts.