FAS/CD95 AND HIV-1 INDUCED HEMATOPATHOLOGY

描述：(改编自申请摘要)细胞凋亡，或 程序性细胞死亡，外周血淋巴细胞已收到 注意是HIV-1耗尽T淋巴细胞的可能机制。 可想而知，在HIV-L感染的背景下淋巴细胞的凋亡 由几种机制引起，包括CD4交联化，上调 Fas(APO1，CD95)是细胞内“死亡信号”的受体和传导者， 和/或上调Fas配体。更深入地了解黑猩猩的生物学 Fas对淋巴细胞中的Fas具有非凋亡的调节功能 发展，这表明可能的机制，而不是细胞死亡通过 哪种病毒可能会产生病理效应。 这项研究的中心假设是HIV-1可能改变这种调节 Fas及其配体在中央血淋巴器官中的表达 干扰血统的发展。使用SCID-HU THY/LIV和SCID-HU 骨系统作为造血和HIV-1感染模型的实验 我将首先讨论HIV-1感染对Fas表达的影响 关于造血细胞和淋巴细胞的荧光分选亚群 祖细胞。HIV-1诱导的改变的功能后果 然后将使用造血功能的分析来研究Fas的作用， 增殖和TCR信号。

DESCRIPTION: (Adapted from the application abstract) Apoptosis, or programmed cell death, of peripheral blood lymphocytes has received attention as a possible mechanism whereby HIV-1 may deplete T lymphocytes. Apoptosis of lymphocytes in the setting of HIV-l infection could conceivably arise by several mechanisms, including CD4 cross-linking, upregulation of Fas (APO1, CD95) the cellular receptor and transducer of the "death signal", and/or upregulation of Fas ligand. A deeper understanding of the biology of Fas has revealed a non-apoptotic, regulatory function for Fas in lymphocyte development, which suggests possible mechanisms other than cell death by which virus may exert pathological effects. The central hypthesis of this study is that HIV-1 may alter the regulation of Fas and its ligand in central hematolymphoid organs, and thereby interfere with lineage development. Employing SCID-hu Thy/Liv and SCID-hu Bone systems as models of hemetopoiesis and of HIV-1 infection, experiments will first address the effects of HIV-1 infection on the expression of Fas on fluorescence-sorted subpopulations of hematopoietic and lymphocyte progenitor cells. The funcitonal consequences of HIV-1-induced alterations of Fas will then be studied using assays of hematopoietic funciton, proliferation, and TCR signaling.