美国Tulane国立灵长类动物研究中心一项研究探索了猿免疫缺陷病毒(SIV)与导致结核病(TB)的结核分枝杆菌(Mtb)联合感染的一个猕猴模型的保护性免疫机制。每3人就有1人有潜伏的结核分支杆菌(Mtb)，它可能发展成活动的结核病。它与人类免疫缺陷病毒(HIV)的联合感染可能让潜伏结核病变为活动结核病的进程加速，这个过程很可能是由CD4+ t细胞耗尽驱动的。为了研究人类免疫缺陷病毒(HIV)免疫调控的潜伏结核病感染，Deepak Kaushal及其同事用结核分枝杆菌(Mtb)和猿免疫缺陷病毒(SIV)感染了猕猴，模仿了人类的结核分枝杆菌(Mtb)与人类免疫缺陷病毒(HIV)联合感染。在多数动物中，结核分枝杆菌(Mtb)的复制迅速重新激活，并且发展成了活动结核病，而且与猿免疫缺陷病毒(SIV)有关的病理增加。尽管所有被联合感染的猕猴的肺CD4+ T细胞减少，其中1/3的猕猴仍然维持了潜伏结核病。对于这个群体，由CD8+记忆T细胞增殖以及b细胞应答增加调控的保护性免疫应答的增加，与有限的结核分枝杆菌(Mtb)复制有关联。这组作者说，这些发现可能为结核分枝杆菌(Mtb)的天然免疫力提供了见解，而且可能有助于指导结核病与人类免疫缺陷病毒(HIV)的疫苗与免疫疗法的开发。

原文摘要：The synergy between Mycobacterium tuberculosis (Mtb) and HIV in coinfected patients has profoundly impacted global mortality because of tuberculosis (TB) and AIDS. HIV significantly increases rates of reactivation of latent TB infection (LTBI) to active disease, with the decline in CD4+ T cells believed to be the major causality. In this study, nonhuman primates were coinfected with Mtb and simian immunodeficiency virus (SIV), recapitulating human coinfection. A majority of animals exhibited rapid reactivation of Mtbreplication, progressing to disseminated TB and increased SIV-associated pathology. Although a severe loss of pulmonary CD4+ T cells was observed in all coinfected macaques, a subpopulation of the animals was still able to prevent reactivation and maintain LTBI. Investigation of pulmonary immune responses and pathology in this cohort demonstrated that increased CD8+ memory T-cell proliferation, higher granzyme B production, and expanded B-cell follicles correlated with protection from reactivation. Our findings reveal mechanisms that control SIV- and TB-associated pathology. These CD4-independent protective immune responses warrant further studies in HIV coinfected humans able to control their TB infection. Moreover, these findings will provide insight into natural immunity to Mtb and will guide development of novel vaccine strategies and immunotherapies.