Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America.
PLoS Pathog. 2011 Oct;7(10):e1002288. doi: 10.1371/journal.ppat.1002288. Epub 2011 Oct 6.
Homeostatic proliferation ensures the longevity of central memory T-cells by inducing cell proliferation in the absence of cellular differentiation or activation. This process is governed mainly by IL-7. Central memory T-cells can also be stimulated via engagement of the T-cell receptor, leading to cell proliferation but also activation and differentiation. Using an in vitro model of HIV-1 latency, we have examined in detail the effects of homeostatic proliferation on latently infected central memory T cells. We have also used antigenic stimulation via anti-CD3/anti-CD28 antibodies and established a comparison with a homeostatic proliferation stimulus, to evaluate potential differences in how either treatment affects the dynamics of latent virus populations. First, we show that homeostatic proliferation, as induced by a combination of IL-2 plus IL-7, leads to partial reactivation of latent HIV-1 but is unable to reduce the size of the reservoir in vitro. Second, latently infected cells are able to homeostatically proliferate in the absence of viral reactivation or cell differentiation. These results indicate that IL-2 plus IL-7 may induce a detrimental effect by favoring the maintenance of the latent HIV-1 reservoir. On the other hand, antigenic stimulation efficiently reactivated latent HIV-1 in cultured central memory cells and led to depletion of the latently infected cells via virus-induced cell death.
稳态增殖通过在没有细胞分化或激活的情况下诱导细胞增殖来确保中央记忆 T 细胞的长寿。这个过程主要由 IL-7 控制。中央记忆 T 细胞也可以通过 T 细胞受体的结合被刺激，导致细胞增殖，但也会导致激活和分化。我们使用 HIV-1 潜伏的体外模型，详细研究了稳态增殖对潜伏感染的中央记忆 T 细胞的影响。我们还通过抗 CD3/抗 CD28 抗体进行了抗原刺激，并与稳态增殖刺激物进行了比较，以评估这两种处理方式如何影响潜伏病毒群体的动态。首先，我们表明，由 IL-2 加 IL-7 诱导的稳态增殖导致潜伏 HIV-1 的部分重新激活，但不能减少体外储库的大小。其次，潜伏感染的细胞能够在没有病毒重新激活或细胞分化的情况下进行稳态增殖。这些结果表明，IL-2 加 IL-7 可能通过有利于潜伏 HIV-1 储库的维持而产生有害影响。另一方面，抗原刺激有效地重新激活了培养的中央记忆细胞中的潜伏 HIV-1，并通过病毒诱导的细胞死亡导致潜伏感染细胞的耗竭。
