Inserm UMR S 945, Infections and Immunity, Avenir Group, Universitě Pierre et Marie Curie-Paris 6, Hôpital Pitiě-Salpêtrière, Paris, France.
Blood. 2011 May 12;117(19):5142-51. doi: 10.1182/blood-2011-01-331306. Epub 2011 Mar 24.
The mechanisms of CD4(+) T-cell count decline, the hallmark of HIV disease progression, and its relationship to elevated levels of immune activation are not fully understood. Massive depletion of CD4(+) T cells occurs during the course of HIV-1 infection, so that maintenance of adequate CD4(+) T-cell levels probably depends primarily on the capacity to renew depleted lymphocytes, that is, the lymphopoiesis. We performed here a comprehensive study of quantitative and qualitative attributes of CD34(+) hematopoietic progenitor cells directly from the blood of a large set of HIV-infected persons compared with uninfected donors, in particular the elderly. Our analyses underline a marked impairment of primary immune resources with the failure to maintain adequate lymphocyte counts. Systemic immune activation emerges as a major correlate of altered lymphopoiesis, which can be partially reversed with prolonged antiretroviral therapy. Importantly, HIV disease progression despite elite control of HIV replication or virologic success on antiretroviral treatment is associated with persistent damage to the lymphopoietic system or exhaustion of lymphopoiesis. These findings highlight the importance of primary hematopoietic resources in HIV pathogenesis and the response to antiretroviral treatments.
CD4(+) T 细胞计数下降的机制是 HIV 疾病进展的标志，其与免疫激活水平升高的关系尚未完全阐明。在 HIV-1 感染过程中会发生大量的 CD4(+) T 细胞耗竭，因此维持足够的 CD4(+) T 细胞水平可能主要取决于补充耗竭淋巴细胞的能力，即淋巴生成。我们在这里对大量 HIV 感染者与未感染者（尤其是老年人）的血液中的 CD34(+)造血祖细胞的定量和定性特征进行了综合研究。我们的分析强调了原发性免疫资源的明显受损，导致淋巴细胞计数无法维持在适当水平。系统性免疫激活是淋巴生成改变的主要相关因素，长期抗逆转录病毒治疗可部分逆转这种改变。重要的是，尽管 HIV 复制得到精英控制或抗逆转录病毒治疗取得病毒学成功，但 HIV 疾病的进展仍与淋巴生成系统的持续损伤或淋巴生成衰竭有关。这些发现强调了原发性造血资源在 HIV 发病机制和抗逆转录病毒治疗反应中的重要性。
