CD34+ PROGENITOR IN PATHOGENESIS OF AIDS KAPOSI SARCOMA

艾滋病相关性卡波西肉瘤（AIDS associated Kaposi's Sarcoma，AIDS-KS）仍是主要的艾滋病之一 艾滋病毒感染的同性恋者的相关病理。AIDS-KS肿瘤是 由新生血管形成的多灶性血管生成性病变和梭形 细胞这些梭形细胞具有内皮细胞的标记， 平滑肌细胞和真皮树突状细胞，是肿瘤细胞。 然而，这些细胞在注射到裸鼠体内时不会形成肿瘤， 但尚未确定它们是否已经转化。两大 l）祖细胞类型是什么， 2）KS细胞是转化的，还是 正常细胞被驱动为增殖性血管生成表型，如果它们 都被转化了，转化的媒介是什么？近日，流传着 已经描述了患有这种疾病的患者中类似KS的细胞， 以及一种新的疱疹病毒的DNA片段， 已经分离出非常高百分比的AIDS-KS（KSHV）病变。在 初步研究，研究循环发展的模型 正常人CD 34+祖细胞分化为梭形细胞 KS-细胞，并建立了内皮细胞。发现T细胞 细胞因子影响CD 34+分化，并且含有细胞因子的细胞系 KSHV DNA可以改变CD 34+祖细胞的正常发育， 将KSHV DNA病毒传播至脐带血单核细胞。我们 假设AIDS-KS前体是正常的CD 34+循环细胞 而KS是改变发展的结果， 直接由病毒转化（KSHV）引起的CD 34+前体，或 间接通过细胞因子介导。为了验证这一假设，我们将 富含KSHV和HIV的KS祖细胞的CD 34+细胞群 感染;或T细胞因子释放，以响应那些 感染.我们将检测CD 34衍生的KS样细胞的能力， 和KSHV感染的细胞在体外支持血管生成的能力 并在体内诱导KS损伤;以及在体内形成集落的能力。 软琼脂和裸鼠成瘤。循环的KS祖细胞 将被分离，其表型标志物和体外行为， 将在体内进行研究。这项研究的结果将提供重要的 深入了解AIDS-KS的发病机制，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.