Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
AIDS. 2013 Apr 24;27(7):1059-69. doi: 10.1097/QAD.0b013e32835e2b99.
T regulatory (Treg) cells are a heterogeneous population that consists of CD4(+)CD25(low)CD45RA(+) [naive Treg (nTreg) cells] and CD4(+)CD25(high)CD45RA(-) [activated Treg (aTreg) cells] subsets. We investigated the effects of HIV infection and HAART on distinct Treg subsets.
HIV-infected adult patients naive to HAART (n=57), patients with acute HIV infection (n=13), and healthy controls (n=92) were recruited for a cross-sectional study. Patients receiving HAART were followed up in a longitudinal study.
Compared with healthy controls, we observed a reduced proportion of nTreg cells and an elevated frequency of aTreg cells in peripheral blood from HAART-naïve patients. Moreover, nTreg cells showed a decreased CD31(+) frequency, whereas aTreg cells showed an increased CD31(+) frequency, indicating impaired thymic output and excessive conversion from nTreg to aTreg cells. nTreg and aTreg cells both displayed higher levels of Ki67(+), reflecting hyperproliferation. The longitudinal study showed that HAART successfully recovered nTreg but not aTreg cell frequency. Higher baseline naïve CD4 T-cell percentages were associated with faster reconstitution of nTreg cell frequency as well as CD4(+) T-cell count.
Our data suggest that the disturbed homeostasis of Treg cells in HIV-infected patients is probably caused by excessive conversion from nTreg to aTreg cells, and impaired thymic output of nTreg cells. nTreg cells can be recovered by HAART, which was associated with baseline naive CD4(+) T-cell percentages, indicating that reconstitution of nTreg cells may benefit from earlier antiretroviral treatment.
调节性 T 细胞（Treg）是一个异质性群体，由 CD4(+)CD25(low)CD45RA(+) [幼稚 Treg (nTreg) 细胞] 和 CD4(+)CD25(high)CD45RA(-) [活化 Treg (aTreg) 细胞] 亚群组成。我们研究了 HIV 感染和 HAART 对不同 Treg 亚群的影响。
我们招募了未经 HAART 治疗的 HIV 感染成年患者（n=57）、急性 HIV 感染患者（n=13）和健康对照者（n=92）进行横断面研究。接受 HAART 的患者进行了纵向研究。
与健康对照者相比，我们观察到未经 HAART 治疗的患者外周血中 nTreg 细胞比例降低，aTreg 细胞频率升高。此外，nTreg 细胞 CD31(+)频率降低，而 aTreg 细胞 CD31(+)频率升高，表明胸腺输出受损和 nTreg 向 aTreg 细胞的过度转化。nTreg 和 aTreg 细胞均显示 Ki67(+)水平升高，反映出过度增殖。纵向研究表明，HAART 成功恢复了 nTreg 但未恢复 aTreg 细胞频率。较高的基线幼稚 CD4 T 细胞百分比与 nTreg 细胞频率以及 CD4(+) T 细胞计数的更快恢复相关。
我们的数据表明，HIV 感染患者 Treg 细胞的平衡失调可能是由于 nTreg 向 aTreg 细胞的过度转化以及 nTreg 细胞的胸腺输出受损所致。HAART 可恢复 nTreg 细胞，这与基线幼稚 CD4(+) T 细胞百分比相关，表明 nTreg 细胞的重建可能受益于早期抗逆转录病毒治疗。
