Grelli Sandro, d'Ettorre Gabriella, Lauria Filippo, Montella Francesco, Di Traglia Loide, Lichtner Miriam, Vullo Vincenzo, Favalli Cartesio, Vella Stefano, Macchi Beatrice, Mastino Antonio
Department of Experimental Medicine and Biochemical Science, Tor Vergata University Hospital, 00133 Rome, Italy.
J Antimicrob Chemother. 2004 Mar;53(3):494-500. doi: 10.1093/jac/dkh105. Epub 2004 Feb 12.
We have addressed the relationships between inhibition of CD4+ and CD8+ cell apoptosis and CD4+ cell recovery in HIV patients undergoing potent antiretroviral therapy (PART) by correlating apoptosis levels with virological and immunological parameters detected over a long-term period in HIV patients undergoing therapy.
Twenty-two HIV-1-infected patients undergoing PART were enrolled in a long-term, open longitudinal study. Data derived from 17 patients with successful response to therapy (TS; median time of follow-up 36 months, range 24-36 months) were used for correlation studies. Apoptosis was evaluated after short-term culture of peripheral blood lymphocytes by flow cytometry analysis of isolated nuclei or of annexin V/CD4, annexin V/CD8 double-stained cells.
Sustained, noticeable levels of apoptosis inhibition in peripheral blood mononuclear cells were measured, in the long-term, in 16 of the 17 TS patients. Levels of total cell apoptosis correlated with levels of CD8+ apoptotic cells more significantly than with levels of CD4+ apoptotic cells. In addition, CD4+ cell counts were correlated inversely with levels of CD8+ apoptotic cells in a highly significant fashion, but not with levels of CD4+ apoptotic cells.
Our data indicate that the increase of CD4+ lymphocytes in HIV patients, as a consequence of successful response to PART, may be related to changes in apoptosis level occurring in the CD8+, and not in the CD4+, cell compartment.
我们通过将接受高效抗逆转录病毒治疗(PART)的HIV患者的凋亡水平与长期检测的病毒学和免疫学参数相关联,探讨了CD4 +和CD8 +细胞凋亡抑制与CD4 +细胞恢复之间的关系。
22例接受PART治疗的HIV-1感染患者被纳入一项长期的开放性纵向研究。来自17例治疗反应成功的患者(TS;中位随访时间36个月,范围24 - 36个月)的数据用于相关性研究。通过对分离的细胞核或膜联蛋白V/CD4、膜联蛋白V/CD8双染细胞进行流式细胞术分析,对外周血淋巴细胞进行短期培养后评估凋亡情况。
长期来看,17例TS患者中有16例外周血单个核细胞中检测到持续且显著的凋亡抑制水平。总细胞凋亡水平与CD8 +凋亡细胞水平的相关性比与CD4 +凋亡细胞水平的相关性更显著。此外,CD4 +细胞计数与CD8 +凋亡细胞水平呈高度显著的负相关,但与CD4 +凋亡细胞水平无关。
我们的数据表明HIV患者因对PART治疗反应成功而导致的CD4 +淋巴细胞增加,可能与CD8 +细胞区室而非CD4 +细胞区室中发生的凋亡水平变化有关。