DENDRITIC CELL/T-CELL INTERACTIONS IN ALLOGENEIC TRANSPLANTATION

树突状细胞是骨髓源性的白细胞， 专门捕获抗原和初始T细胞介导的免疫 回应。树突状细胞表达高水平的抗原 介绍MHC产品以及一些配件 调节T细胞结合和共刺激的分子。 树突状细胞代表一种独特的造血细胞途径 分化，在这个过程中，许多属性 吞噬细胞被牺牲，以换取它们非常高的水平 MHC产品和辅助分子。这些都是基础 树突状细胞高效的抗原提呈和活化 静止的T细胞。活性细胞因子的鉴定及相关研究进展 树突状细胞的特异性祖细胞促进了 这些生理佐剂的实验研究 正常的和病理的细胞介导的免疫反应。 因此，本课题将应用这些方法来研究 同种异体移植中树突状C-T细胞相互作用的研究 移植。CFU-DC含量将与 不同来源的可移植造血干细胞， 按年龄分层以确定人类在多大程度上 生命早期的树突状细胞不同于成年树突状细胞 在可比水平的刺激能力方面 差异化。CFU的内容和候选人的发展 淋巴树突状细胞也将被研究，因为这些可能 事实证明，与髓系细胞相比，外周血耐受更具相关性 树突状细胞。免疫后T细胞的MHC限制 然后将根据动力学对移植进行评估 和供者树突状细胞植入比例，并进行比较 临床结果参数。初步研究将利用 单倍体相合的同种异体父母移植的长期存活者 先天性免疫缺陷，但焦点最终将是 血液病患者接受不匹配同种异体移植的体会 恶性肿瘤。从头开始和召回抗原将被评估为 在移植中区分供者来源的T淋巴细胞后代 宿主，来自残留宿主或移植的供体克隆。最后， 树突状细胞在诱导移植物抗白血病中的作用 将研究与GVH/HVG反应无关的响应 接受同种异体移植治疗慢性阻塞性肺疾病的患者 骨髓性白血病。树突状细胞的免疫原性 产生抗自体抗原特异性CTL的细胞 表达融合基因多肽的白血病细胞也将 学习。

Dendritic cells are bone marrow-derived leukocytes that are specialized to capture antigen and initial T cell-mediated immune responses. Dendritic cells express high levels of antigen presenting MHC products, as well as a number of accessory molecules that mediate T cell binding and costimulation. Dendiritic cells represent a distinct pathway of hematopoietic differentiation, during which many of the properties of phagocytes are sacrificed in exchange for their very high levels of MHC products and accessory molecules. These underlie dendritic cells efficient antigen presentation and activation of quiescent T cells. The identification of active cytokines and specific progenitors for dendritic cells have advanced the experimental study of these physiologic adjuvants in the context of normal and pathologic cell mediated immune responses. The subject will therefore apply these approaches to study dendritic c-T cell interactions in the setting of allogeneic transplantation. CFU-DC content will be compared between different transplantable sources of hematopoietic stem cells, stratified by age to ascertain the degree to which human dendritic cells early in life differ from adult counterparts with respect to stimulatory capacity at comparable levels of differentiation. The CFU content and development of candidate lymphoid dendritic cells will also be investigated, as these may prove more relevant to peripheral tolerance than myeloid dendritic cells. The MHC restriction of T cells emerging post- transplant will then be evaluated with respect to the kinetics and proportion of donor dendritic cell engraftment, and compared to clinical outcome parameters. Initial studies will utilize long term survivors of haploidentical parental allografts for congenital immunodeficiencies, but the focus will ultimately be on patients receiving mismatched allografts for hematologic malignancies. De novo and recall antigens will be assessed to distinguish donor-derived T lymphoid progeny in the engrafted host, from residual host or transplanted donor clones. Finally, the role of dendritic cells in eliciting a graft-vs-leukemia response, independent of GvH/HvG reactions, will be investigated in patients undergoing allogeneic transplantation for chronic myelogenous leukemia. The immunogenic potential of dendritic cells to generate autologous antigen specific CTL against leukemia cells expressing fusion gene peptides will also be studied.