Tulane National Primate Research Center, Covington, Louisiana, USA.
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA.
J Clin Invest. 2019 Dec 2;129(12):5254-5260. doi: 10.1172/JCI125810.
HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4+ T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4+ T cells during infection failed to reactivate TB. To investigate the contribution of CD4+ T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4+ T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4+ T cells during LTBI was insufficient in generating reactivation of LTBI. Instead, direct cytopathic effects of SIV resulting in chronic immune activation, along with the altered effector T cell phenotypes and dysregulated T cell homeostasis, were likely mediators of reactivation of LTBI. These results revealed important implications for TB control in HIV-coinfected individuals.
HIV 是结核病（TB）复发的主要驱动因素。人们认为，潜伏性结核感染（LTBI）合并 HIV 感染的个体中 CD4+T 细胞耗竭是 TB 复发的基础。感染不会导致组织 CD4+T 细胞耗竭的突变性猿猴免疫缺陷病毒（SIVΔGY）的非人类灵长类动物（NHPs）未能使 TB 复发。为了研究 CD4+T 细胞耗竭相对于 SIV 诱导 LTBI 复发的其他机制的贡献，我们在未感染慢病毒的 LTBI 动物中使用 CD4R1 抗体耗尽 CD4+T 细胞。LTBI 期间单纯耗尽 CD4+T 细胞不足以引发 LTBI 的复发。相反，SIV 导致的直接细胞病变作用导致慢性免疫激活，以及效应 T 细胞表型的改变和 T 细胞稳态的失调，可能是 LTBI 复发的介导物。这些结果对 HIV 合并感染个体的结核病控制具有重要意义。
