Airò P, Torti C, Uccelli M C, Malacarne F, Palvarini L, Carosi G, Castelli F
Department of Clinical Immunology, University of Brescia, Italy.
AIDS Res Hum Retroviruses. 2000 Nov 20;16(17):1805-7. doi: 10.1089/08892220050195766.
The mechanism causing the increasing number of peripheral T cells after highly active antiretroviral therapy (HAART) is still unclear. The bcl-2 oncogene prevents spontaneous apoptosis (SA) in lymphocytes. Spontaneous apoptosis could be a determinant of HIV immunodeficiency and can be reversed by HAART including protease inhibitors (PI-HAART). The aims of our study were to measure Bcl-2 protein expression in memory (CD45RO+) and naive (CD45RO-) CD4+ and CD8+ T lymphocytes of HIV+ patients and to correlate it with efficacy of PI-HAART. Forty-nine HIV+ patients (cases) and 26 HIV- individuals (controls) were evaluated. Patients receiving PI-HAART, and who had undetectable HIV plasma viral load (VL-, n = 21), had higher levels of Bcl-2 than did VL+ patients (n = 28), both in CD4+ cells (p < 0.0001) and in CD8+ cells (p < 0.001). VL+ patients had lower Bcl-2 levels than did controls in CD8+ cells (p = 0.02), but not in CD4+ cells (p > 0.05). Interestingly, VL- patients had higher Bcl-2 expression than did controls both in CD4+ cells (p < 0.0001) and in CD8+ cells (p = 0.03). In a subcohort of the same patients, Bcl-2 was significantly higher in VL- patients (n = 10) than in controls (n = 12), both in naive CD4+ cells (p < 0.0001) and in naive CD8+ cells (p = 0.01). Naive CD4+ cells had higher Bcl-2 expression in VL- than in VL+ patients (p = 0.01). In a subsequent longitudinal study of nine HIV patients, naive CD4+ cells increased after effective PI-HAART (p = 0.03), which paralleled an increase in Bcl-2 expression in the same cells (p = 0.02). In conclusion, upregulation of bcl-2 could be a mechanism of immune reconstitution of naive CD4+ T cells induced by PI-HAART.
高效抗逆转录病毒疗法（HAART）后外周血T细胞数量增加的机制仍不清楚。bcl-2癌基因可防止淋巴细胞发生自发凋亡（SA）。自发凋亡可能是HIV免疫缺陷的一个决定因素，并且可以通过包括蛋白酶抑制剂的HAART（PI-HAART）来逆转。我们研究的目的是检测HIV阳性患者记忆性（CD45RO+）和初始（CD45RO-）CD4+及CD8+ T淋巴细胞中Bcl-2蛋白的表达，并将其与PI-HAART的疗效相关联。对49例HIV阳性患者（病例组）和26例HIV阴性个体（对照组）进行了评估。接受PI-HAART且血浆HIV病毒载量检测不到（VL-，n = 21）的患者，其CD4+细胞（p < 0.0001）和CD8+细胞（p < 0.001）中的Bcl-2水平均高于病毒载量阳性（VL+）患者（n = 28）。VL+患者CD8+细胞中的Bcl-2水平低于对照组（p = 0.02），但CD4+细胞中的Bcl-2水平与对照组无差异（p > 0.05）。有趣的是，VL-患者CD4+细胞（p < 0.0001）和CD8+细胞（p = 0.03）中的Bcl-2表达均高于对照组。在同一批患者的一个亚组中，VL-患者（n = 10）初始CD4+细胞（p < 0.0001）和初始CD8+细胞（p = 0.01）中的Bcl-2水平均显著高于对照组（n = 12）。初始CD4+细胞中，VL-患者的Bcl-2表达高于VL+患者（p = 0.01）。在随后对9例HIV患者进行的纵向研究中，有效的PI-HAART治疗后初始CD4+细胞数量增加（p = 0.03），同时这些细胞中Bcl-2表达也增加（p = 0.02）。总之，bcl-2上调可能是PI-HAART诱导初始CD4+ T细胞免疫重建的一种机制。
