CD34+ PROGENITOR IN PATHOGENESIS OF AIDS KAPOSI SARCOMA

艾滋病相关卡波西肉瘤(AIDS-KS)仍然是主要的艾滋病之一 感染艾滋病毒的同性恋者的相关病理。艾滋病-KS肿瘤是 新生血管和梭形血管形成的多灶性血管新生病变 细胞。这些梭形细胞有内皮细胞的标记， 平滑肌细胞和真皮树突状细胞是肿瘤细胞 然而，当这些细胞注射到裸鼠体内时，并不形成肿瘤。 目前还没有确定它们是否被改造了。两大 问题仍然悬而未决L)什么是祖细胞类型？ 驱动这些细胞到KS的因素2)KS细胞是转化的还是他们 正常细胞被驱使到增殖的血管生成表型，如果他们 都被转化了，转化的媒介是什么？最近，正在流传的 已经描述了这种疾病患者中类似KS的细胞， 以及一种新的疱疹病毒的DNA片段，该病毒与 已经分离出了非常高比例的艾滋病-KS(KSHV)病变。在……里面 初步研究，一个研究流通领域发展的模型 正常人CD34+祖细胞分化为类纺锤形细胞 KS-细胞，并向内皮细胞分化。研究发现，T细胞 细胞因子影响CD34+的分化，细胞系含有 KSHV DNA可改变CD34+祖细胞的正常发育 通过病毒途径将KSHV DNA传递给脐带血单个核细胞。我们 假设AIDS-KS前体细胞是正常的CD34+循环细胞 而KS是发展变化的结果 病毒转化(KSHV)或直接引起CD34+前体 间接地通过细胞因子介体。为了检验这一假设，我们将揭示 KSHV和HIV的KS祖细胞中富含CD34+细胞群 感染；或对T细胞细胞因子的反应 感染。我们将检测CD34来源的KS样细胞的能力 和KSHV感染细胞在体外支持血管生成的能力 并在体内诱导KS损伤；在体内形成克隆的能力 软琼脂，诱发裸鼠肿瘤。循环中的KS祖细胞 将被分离出来，其表型标志和体外行为 将在体内进行研究。这项研究的结果将提供重要的 对AIDS-KS发病机制的洞察并将促进 艾滋病-KS的新机制和干预研究。

AIDS associated Kaposi's Sarcoma (AIDS-KS) is still one of the major AIDS associated pathologies in HIV infected homosexuals. AIDS-KS tumors are multifocal angiogenic lesions formed by neovasculature and spindle shaped cells. These spindle shaped cells have markers for endothelial cells, smooth muscle cells and dermal dendrocytes and are the "tumor cell" in KS; however these cells don't form tumors when injected in nude mice and it has not been firmly establish whether they are transformed. Two major issues are still unresolved l) What is the progenitor cell type and what factors drive these cells to KS 2) Are KS cells transformed or are they normal cells driven to a proliferative angiogenic phenotype, and if they are transformed, what are the transforming agents? Recently, circulating cells resembling KS in patients with this disorder have been described, and a DNA fragment from a new class of herpes virus associated with a very high percentage of AIDS-KS (KSHV) lesions has been isolated. In preliminary studies, a model to study the development of circulating normal human CD34+ progenitors cells into spindle shaped cells resembling KS-cells, and to endothelium was established. It was found that T-cell cytokines affect CD34+ differentiation and a cell line containing the KSHV DNA can alter both the normal development of CD34+ progenitors and virally-transmit KSHV DNA to umbilical cord blood mononuclear cells. We postulate that the AIDS-KS precursor is a normal CD34+ circulating cell and that KS is the result of an alteration of the development in the CD34+ precursor caused directly by viral transformation (KSHV) or indirectly by cytokine mediators. To test this hypothesis we will expose CD34+ cell populations enriched in KS progenitors to KSHV and HIV infection; or to the T-cell cytokines released in response to those infections. We will examine the ability of the CD34-derived KS-like cells and KSHV infected cells in their ability to support angiogenesis in vitro and to induce KS-lesions in vivo; and the ability to form colonies in soft agar and induce tumors in nude mice. The circulating KS progenitor will be isolated and its phenotypical markers and behavior in vitro and in vivo will be studied. The results of this study will provide important insights into the pathogenesis of AIDS-KS and will foster development of novel mechanistic and intervention studies for AIDS-KS.