Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA.
J Clin Immunol. 2010 Sep;30(5):681-92. doi: 10.1007/s10875-010-9432-3. Epub 2010 Jun 23.
Little is known about the manipulation of IL-17 producing CD4+ T cells (T(H)17) on a per-cell basis in humans in vivo. Previous studies on the effects of IL-2 on IL-17 secretion in non-HIV models have shown divergent results. We hypothesized that IL-2 would mediate changes in IL-17 levels among recently HIV-1-infected adults receiving anti-retroviral therapy. We measured cytokine T cell responses to CD3/CD28, HIV-1 Gag, and CMV pp65 stimulation, and changes in multiple CD4+ T cell subsets. Those who received IL-2 showed a robust expansion of naive and total CD4+ T cell counts and T-reg counts. However, after IL-2 treatment, the frequency of T(H)17 cells declined, while counts of T(H)17 cells did not change due to an expansion of the CD4+ naïve T cell population (CD27+CD45RA+). Counts of HIV-1 Gag-specific T cells declined modestly, but CMV pp65 and CD3/CD28 stimulated populations did not change. Hence, in contrast with recent studies, our results suggest IL-2 is not a potent in vivo regulator of T(H)17 cell populations in HIV-1 disease. However, IL-2-mediated T-reg expansions may selectively reduce responses to certain antigen-specific populations, such as HIV-1 Gag.
目前对于在活体人类中以单细胞水平对产生白介素 17 的 CD4+T 细胞（T(H)17）进行操控知之甚少。之前在非 HIV 模型中对于白介素 2 对 IL-17 分泌影响的研究结果存在分歧。我们假设白介素 2 将介导接受抗逆转录病毒治疗的新近 HIV-1 感染者的 IL-17 水平变化。我们测量了细胞因子 T 细胞对 CD3/CD28、HIV-1 Gag 和 CMV pp65 刺激的反应，以及多个 CD4+T 细胞亚群的变化。接受白介素 2 治疗的患者表现出幼稚和总 CD4+T 细胞计数和 T 调节细胞计数的显著增加。然而，在白介素 2 治疗后，T(H)17 细胞的频率下降，而由于 CD4+幼稚 T 细胞群体（CD27+CD45RA+）的扩张，T(H)17 细胞的计数没有改变。HIV-1 Gag 特异性 T 细胞的计数略有下降，但 CMV pp65 和 CD3/CD28 刺激的群体没有变化。因此，与最近的研究结果相反，我们的结果表明白介素 2 不是 HIV-1 疾病中 T(H)17 细胞群体的有效体内调节剂。然而，白介素 2 介导的 T 调节细胞的扩张可能会选择性地降低对某些抗原特异性群体的反应，例如 HIV-1 Gag。
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