DONOR CD8 EFFECTOR FUNCTION IN MARROW TRANSPLANTATION

描述(改编自申请人的摘要)：长期目标 这个项目的目的是确定一群捐赠者T细胞， 用于预防移植物排斥反应，而无需显著的移植物抗宿主作用 异基因骨髓移植后的疾病。为了 评估使用CD8细胞确保植入的可行性，而不是 导致GVHD的供者CD8+T细胞的表型和功能必须 已经成立了。调查人员将测试：(1)所需细胞是否 必须具有细胞毒性，(2)同种异体抗原是否仅在 淋巴造血细胞是比广义的更有效的靶点 表达同种异体抗原，(3)低亲和力TCR的T细胞是否 优于具有高亲和力TCR的T细胞，以及(4)供者T细胞 必须迁移并回到淋巴结，以防止排斥反应。在……里面 此外，还将测试受者异体免疫的作用。 识别CD8群体可以在没有排斥的情况下防止排斥反应 在小鼠身上引起移植物抗宿主病将导致在 人类。这些结果不仅对同种异体基因具有重要意义 同时也为骨髓移植设计了新的领养方式 免疫疗法。

DESCRIPTION (Adapted from the Applicant's Abstract): The long term goal of this project is to identify a population of donor T cells that can be used to prevent graft rejection without significant graft versus host disease after allogeneic bone marrow transplantation. In order to assess the feasibility of using CD8 cells to assure engraftment without causing GVHD, the phenotype and function of donor CD8+ T cells must be established. The investigator will test: (1) whether the desired cell must be cytotoxic, (2) whether alloantigens expressed only on lymphohematopoietic cells are more effective targets than broadly expressed alloantigens, (3) whether T cells with low affinity TCR are better than T cells with high affinity TCR, and (4) whether donor T cells must migrate and home to lymph nodes in order to prevent rejection. In addition, the role of alloimmunization of the recipient will be tested. Identification of a CD8 population that can prevent rejection without causing GVHD in mice will lead to the testing of similar approaches in humans. These results will be of importance not only for allogeneic bone marrow transplantation but also for the design of novel adoptive immunotherapies.