IMMUNOBIOLOGY OF HYBRID RESISTANCE

骨髓细胞移植是一种成功的治疗方法。 白血病、再生障碍性贫血、严重联合免疫缺陷(SCID)、 甚至一些实体组织肿瘤。同种异体骨髓间充质干细胞移植3例 主要并发症：移植失败或排斥、移植物抗宿主 疾病(移植物抗宿主病)和疾病复发。外周血中T细胞的消耗 骨髓通常可以预防严重的移植物抗宿主病，但增加了 疾病的排斥和复发，例如白血病。T细胞耗尽 (TCD)如果能防止排斥反应和白血病，骨髓基质细胞将是一个选择 复发，因为移植物抗宿主病将得到改善。这样做的目的是 建议分析这些宿主效应细胞，以防止 植入，并制定战略，允许在#年植入中药BMC 一个小鼠模型。宿主NK细胞识别“隐性遗传” 干细胞上的造血组织相容性(HH-1)抗原的基础 杂种一代对BMC嫁接的抗性。宿主CD8+T细胞识别类 供体干细胞上的I抗原。具体目标：1.NK细胞的特性 它能识别特定的HH-1抗原。克隆基因 NK标志物5E6和10A7与BMC特异性排斥反应相关 分别表达HH-1决定簇2和5。生产转基因产品 以测试5E6和/或1OA7是特异性NK受体的想法。2. 分析TCD-BMC对排斥反应更敏感的机制 并制定战略，在不导致GVHD的情况下实现增长。测试 想法I)髓系干细胞被NK细胞或新生的 致敏T细胞；ii)供体T细胞抑制宿主效应；以及iii) 宿主T细胞排斥供体T细胞。骨髓T细胞的特性 通过逆流淋洗从干细胞中分离出来后， 临床上用于预防移植物抗宿主病的技术。确定的性质是 通过细胞转移研究排斥供体T细胞的宿主T细胞 去除T细胞的SCID宿主小鼠。3.建立骨髓单个核细胞的体外检测方法 排斥反应，以便更好地评估这些免疫细胞的相互作用。 本研究可为临床骨髓细胞移植提供相关数据。

Bone marrow cell (BMC) transplantation is a successful treatment modality for leukemia, aplastic anemia, severe combined immunodeficiency (SCID), and even some solid tissue tumors. Transfer of allogeneic BMC presents 3 major complications: failure to engraft or rejection, graft-versus-host disease (GVHD) and recurrence of disease. Depletion of T cells from the marrow prevents serious GVHD often, but increases the likelihood for rejection and recurrence of disease, e.g. leukemia. T cell depleted (TCD) BMC would be the choice if one could prevent rejection and leukemia recurrence, since GVHD would be ameliorated. The purpose of this proposal is to analyze those host effector cells which prevent engraftment, and to develop strategies to allow engraftment of TCD BMC in a murine model. Host NK cells recognize 'recessively inherited' Hemopoietic histocompatibility (Hh-1) antigens on stem cells, the basis of Fl hybrid resistance to BMC grafts. Host CD8+ T cells recognize class I antigens on donor stem cells. Specific Aims: 1. Characterize NK cells which recognize specific Hh-1 antigens specifically. Clone the genes for the NK markers 5E6 and 1OA7 associated with the specific rejection of BMC expressing Hh-1 determinants 2 and 5, respectively. Produce transgenic mice to test the idea that 5E6 and/or 1OA7 are specific NK receptors. 2. Analyze the mechanisms by which TCD BMC are more sensitive to rejection and develop strategies to allow growth without causing GVHD. Test the ideas i) myeloid stem cells are rejected by NK cells or by newly sensitized T cells; ii) donor T cells inhibit host effectors; and iii) host T cells reject those donor T cells. Characterize marrow T cell after separation from stem cells by counter current elutriation, a technique used clinically to prevent GVHD. Determine the nature of the host T cell that rejects donor T cells by cell transfer studies involving T cell-deprived SCID host mice. 3. Develop an in vitro assay for BMC rejection to allow better evaluation of these immune cell interactions. This work may provide data relevant to clinical BMC transplantation.