Bi Xiuqiong, Suzuki Yasuhiro, Gatanaga Hiroyuki, Oka Shinichi
AIDS Clinical Center, International Medical Center of Japan, Tokyo, Japan.
Eur J Immunol. 2009 Jan;39(1):301-9. doi: 10.1002/eji.200838667.
The frequency of Treg is reported to be higher in patients with chronic HIV type 1 (HIV-1) infection and CD45RA(+) Treg exist in normal adults. In this study, we found a lower absolute number (15 cells/microL) but a higher proportion (16.2%) of FOXP3(+) cells (Treg) in the CD4(+) population in treatment-naïve HIV-1 patients with low CD4 (<200 cells/microL) counts than in those with high CD4 counts (34 cells/microL and 9.3%) or healthy adults (48 cells/microL and 7.5%). In HIV-1 patients, CD45RA(+)CCR7(+), CD45RA(-)CCR7(+), and CD45RA(-)CCR7(-) subsets were identified in the Treg population, and the proportion of CD45RA(-)CCR7(-) Treg was higher (57.9%) in patients with low CD4 than high CD4 counts (38.3%). Treg were in a high proliferation state especially in patients with low CD4 counts. HIV viral load correlated positively with the Treg proliferation rate and the proportion of CD45RA(-)CCR7(-) Treg. Furthermore, the proliferation of Treg correlated positively with the CD45RA(-)CCR7(-) Treg proportion but negatively with Treg numbers. Successful antiretroviral therapy resulted in a limited increase in Treg numbers, but their frequency was reduced in 1-2 months due to a rapid rebound of FOXP3(-) CD4(+)cells. Our results suggest that HIV-activating Treg may be a reason for the high frequencies of Treg and CD45RA(-)CCR7(-) Treg in the peripheral blood of late-stage HIV-1-infected patients.
据报道，慢性1型人类免疫缺陷病毒（HIV-1）感染患者体内调节性T细胞（Treg）频率较高，且正常成年人中存在CD45RA(+) Treg。在本研究中，我们发现，未接受过治疗、CD4细胞计数低（<200个/微升）的HIV-1患者，其CD4(+)群体中FOXP3(+)细胞（Treg）的绝对数量较低（15个/微升），但比例较高（16.2%），低于CD4细胞计数高的患者（34个/微升和9.3%）或健康成年人（48个/微升和7.5%）。在HIV-1患者中，Treg群体可分为CD45RA(+)CCR7(+)、CD45RA(-)CCR7(+)和CD45RA(-)CCR7(-)亚群，CD4细胞计数低的患者中CD45RA(-)CCR7(-) Treg的比例较高（57.9%），高于CD4细胞计数高的患者（38.3%）。Treg处于高增殖状态，尤其是CD4细胞计数低的患者。HIV病毒载量与Treg增殖率以及CD45RA(-)CCR7(-) Treg的比例呈正相关。此外，Treg的增殖与CD45RA(-)CCR7(-) Treg的比例呈正相关，但与Treg数量呈负相关。成功的抗逆转录病毒治疗使Treg数量有有限增加，但其频率在1 - 2个月内降低，原因是FOXP3(-) CD4(+)细胞迅速反弹。我们的结果表明，HIV激活Treg可能是晚期HIV-1感染患者外周血中Treg和CD45RA(-)CCR7(-) Treg频率较高的原因。
