Memory T Cells in Tumpr Immunity

T细胞可在非消融性T细胞移植(HSPCT)后存活 消融性预适应方案，例如抗辐射T细胞，介导了对造血移植物的抵抗 和感染。最近的发现表明，记忆性T细胞(TM)应该比幼稚的T细胞更有效地存活下来 这一亚群中增强的抗凋亡调节的结果和在这方面的新的初步发现 建议证明宿主TM移植后的存活和扩张。这个项目中的实验将 回答测试CD8 TM在移植时预适应和/或输注将导致 在宿主T细胞存活增加和抗原特异性免疫增强的早期(重组) 移植免疫舱。实验将检验记忆的存活、扩展和功能 HSPCT后受者中的人群。为了完成这些研究，我们将利用和比较转基因 (OT-I)和非转基因(HBO)抗原特异性TM，包括在 项目2.AIM I中的实验旨在阐明移植参数，包括条件化 在移植模型中T细胞充满或耗尽对宿主记忆细胞存活的影响 这些TM人群。IL-15和IL-7参与TM的维护和扩展将是 使用融合蛋白(核心B)和敲除菌株(核心D)进行检查，实验还将检查 移植后记忆细胞对CD30-CD30L相互作用的影响AIM II中的研究 将检查在重组宿主中存在的重新激活的记忆细胞的能力=S淋巴 车厢。抗原传递将使用同基因宿主APC进行检查，并与同基因宿主APC进行比较 转导代理抗原的肿瘤。Gp96-LG转染体作为抗原载体的有效性 Vehicle将与Project 1一起进行研究，以及与Project一起研究IL-15转基因的肿瘤群体 2.将使用免疫分析(核心C)对重新激活的TM的反应进行功能评估。 最后，AIM III的研究旨在检验记忆群体对肿瘤的反应能力 HSPCT后的抗原。将检查携带肿瘤的接受者将在其中进行注射的模型 尝试在移植后早期增强抗肿瘤反应的疫苗和合作 项目3的研究将检验B细胞缺乏对这些反应的影响。

T cells can survive hematopoietic stem/progenitor cell transplants (HSPCT) following non-ablative and ablative conditioning regimens, for example radioresistant T cells mediate resistance to hematopoietic grafts and infection. Recent findings suggest that memory T cells (TM) should survive more effectively vs. naive cells as a result of enhanced anti-apoptotic regulation in this subset and new preliminary findings in this proposal demonstrate survival and expansion of host TM post-transplant. The experiments in this project will address questions testing the hypothesis that CD8 TM pre-conditioning and/or infused at transplant will result in increased host T cell survival and enhanced antigen-specific immunity in the early (reconstituting) post- transplant immune compartment. Experiments will examine the survival, expansion and function of memory populations in the post-HSPCT recipient. To accomplish these studies we will utilize and compare transgenic (OT-I) and non-transgenic (HBO)antigen specific TM including in vitro derived populations as developed in Project 2. Experiments in aim I are directed to elucidating the transplant parameters including conditioning and T cell replete or depleted inoculum on host memory cell survival in transplant models designed to track these TMpopulations. The involvement of IL-15and IL-7 in the maintenance and expansion of TM will be examined using fusion proteins (Core B) and knock-out strains (Core D) and experiments will also examine the role of CD30-CD30L interaction by memory cells post-transplant together with Project! Studies in aim II will examine the capacity of memory cells present to be reactivated in the reconstituting host=s lymphoid compartment. Antigen delivery will be examined using syngeneic host APC and compared to syngeneic tumors transfected with surrogate antigen. The effectiveness of gp96-lg transfectants as an antigen delivery vehicle will be investigated together with Project 1 as well as IL-15 transfected tumor populations with Project 2. Functional evaluation of responses by reactivated TM will be carried out using immune analysis (Core C). Finally, studies in aim III are designed to examine the ability of memory populations to respond to tumor antigens post-HSPCT. Models will be examined in which recipients bearing tumors will be administered vaccines in attempts to augment anti-tumor responses in the early post-transplant period and collaborative studies with Project 3 will examine effects of B cell deficiency in these responses.