Département d'Immunologie, CHU de Montpellier, Université Montpellier 1, Montpellier, France.
Immunology. 2012 Sep;137(1):89-97. doi: 10.1111/j.1365-2567.2012.03609.x.
Immune activation is a main driver of AIDS- and non-AIDS-linked morbidities in the course of HIV-1 infection. As CCR5, the main HIV-1 co-receptor, is not only a chemokine receptor but also a co-activation molecule expressed at the surface of T cells, it could be directly involved in this immune activation. To test this hypothesis, we measured by flow cytometry the mean number of CCR5 molecules at the surface of non-activated CD4(+) T cells (CCR5 density), which determines the intensity of CCR5 signalling, and the percentage of CD8(+) T cells over-expressing CD38 (CD38 expression), a major marker of immune activation, in the blood of 67 HIV-1-infected, non-treated individuals. CCR5 density was correlated with CD38 expression independently of viral load (P=0.016). CCR5 density remained unchanged after highly active anti-retroviral therapy (HAART) introduction or cessation, whereas CD38 expression decreased and increased, respectively. Moreover, pre-therapeutic CCR5 density was highly predictive (r=0.736, P<10(-4) ) of residual CD38 over-expression after 9 months of HAART. Hence, CCR5 might play an immunological role in HIV-1 infection as a driver of immune activation. This could explain why CCR5 antagonists may have an inhibitory effect on immune activation.
免疫激活是 HIV-1 感染过程中艾滋病和非艾滋病相关疾病的主要驱动因素。作为 HIV-1 的主要共受体 CCR5，它不仅是一种趋化因子受体，也是 T 细胞表面表达的共激活分子，因此它可能直接参与这种免疫激活。为了验证这一假设，我们通过流式细胞术测量了未激活的 CD4(+) T 细胞表面 CCR5 分子的平均数量（CCR5 密度），该数量决定了 CCR5 信号的强度，以及血液中表达 CD38（CD38 表达）的 CD8(+) T 细胞的百分比，这是免疫激活的主要标志物，在 67 名未经治疗的 HIV-1 感染者中进行了测量。CCR5 密度与 CD38 表达独立于病毒载量相关（P=0.016）。在引入高效抗逆转录病毒治疗（HAART）或停止治疗后，CCR5 密度保持不变，而 CD38 表达分别降低和增加。此外，治疗前 CCR5 密度与 HAART 治疗 9 个月后 CD38 过度表达的残余量高度相关（r=0.736，P<10(-4)）。因此，CCR5 可能在 HIV-1 感染中作为免疫激活的驱动因素发挥免疫作用。这可以解释为什么 CCR5 拮抗剂可能对免疫激活具有抑制作用。
