Institut Pasteur, Régulation des infections rétrovirales, Département de Virologie, Paris, France.
AIDS. 2012 Jan 14;26(2):139-48. doi: 10.1097/QAD.0b013e32834e1484.
Persistent immune activation plays a central role in the pathogenesis of HIV disease. Besides natural regulatory T cells (nTregs), 'double negative' T cells shown to exhibit regulatory properties could be involved in the control of harmful immune activation. The aim of this study was to analyze, in patients with primary HIV infection (PHI), the relationship between CD4(+)CD25(+)CD127(low)FoxP3(+) nTregs or CD3(+)CD4(-)CD8(-) double negative T cells and systemic immune activation.
A prospective longitudinal study of patients with early PHI.
Twenty-five patients were included. Relationships between frequency of Treg subsets and T-cell activation, assessed on fresh peripheral blood mononuclear cells, were analyzed using nonparametric tests. Cytokine production by double negative T cells was assessed following anti-CD3/anti-CD28 stimulation.
No relationship was found between T-cell activation and frequencies of nTregs. In contrast, a strong negative relationship was found at baseline between the proportion of double negative T cells and the proportion of activated CD8 T cells coexpressing CD38 and HLA-DR (P = 0.005) or expressing Ki-67 (P = 0.002). In addition, the frequency of double negative T cells at baseline negatively correlated with the frequency of HLA-DR(+)CD38(+)CD8(+) T cells at month 6, defining the immune activation set point (P = 0.031). High proportions of stimulated double negative T cells were found to produce the immunosuppressive cytokines transforming growth factor-β1 and/or IL-10.
The proportion of double negative T cells at baseline was found to be predictive of the immune activation set point. Our data strongly suggest that double negative T cells may control immune activation in PHI. This effect might be mediated through the production of TGF-β1/IL-10 known to downmodulate immune activation.
持续的免疫激活在 HIV 疾病的发病机制中起着核心作用。除了天然调节性 T 细胞（nTregs）外，表现出调节特性的“双阴性”T 细胞可能参与控制有害的免疫激活。本研究旨在分析原发性 HIV 感染（PHI）患者中 CD4+CD25+CD127(low)FoxP3+nTregs 或 CD3+CD4-CD8-T 双阴性 T 细胞与全身免疫激活之间的关系。
一项对早期 PHI 患者的前瞻性纵向研究。
纳入 25 例患者。使用非参数检验分析 Treg 亚群与 T 细胞激活频率之间的关系，通过新鲜外周血单核细胞进行评估。在抗 CD3/抗 CD28 刺激后，评估双阴性 T 细胞的细胞因子产生情况。
未发现 T 细胞激活与 nTregs 频率之间存在关系。相比之下，在基线时，双阴性 T 细胞的比例与表达 CD38 和 HLA-DR（P=0.005）或表达 Ki-67（P=0.002）的激活 CD8 T 细胞的比例之间存在强烈的负相关。此外，双阴性 T 细胞在基线时的频率与第 6 个月时 HLA-DR+CD38+CD8+T 细胞的频率呈负相关，定义了免疫激活设定点（P=0.031）。发现高比例的刺激双阴性 T 细胞产生免疫抑制细胞因子转化生长因子-β1 和/或 IL-10。
基线时双阴性 T 细胞的比例被发现可预测免疫激活设定点。我们的数据强烈表明，双阴性 T 细胞可能控制 PHI 中的免疫激活。这种作用可能通过已知下调免疫激活的 TGF-β1/IL-10 的产生来介导。
