Ortiz Alexandra M, Carnathan Diane G, Yu Joana, Sheehan Katherine M, Kim Peter, Reynaldi Arnold, Vanderford Thomas H, Klatt Nichole R, Brenchley Jason M, Davenport Miles P, Silvestri Guido
Yerkes National Primate Research Center, and Emory Vaccine Center, Emory University, Atlanta, 30322, Georgia, United States of America.
Laboratory of Molecular Microbiology, National Institutes of Health, Bethesda, 20892, Maryland, United States of America.
PLoS One. 2016 May 26;11(5):e0156352. doi: 10.1371/journal.pone.0156352. eCollection 2016.
Aberrant turnover of memory CD4+ T-cells is central to Acquired Immunodeficiency Syndrome (AIDS) progression. Understanding the relationship between the turnover of CD4+ subsets and immunological homeostasis during simian immunodeficiency virus (SIV) infection in natural hosts may provide insight into mechanisms of immune regulation that may serve as models for therapeutic intervention in Human Immunodeficiency Virus (HIV)-infected persons. Sooty mangabeys (SMs) have naturally evolved with SIV to avoid AIDS progression while maintaining healthy peripheral CD4+ T-cell counts and thus represent a model by which therapeutic interventions for AIDS progression might be elucidated. To assess the relationship between the turnover of CD4+ subsets and immunological homeostasis during SIV infection in non-progressive hosts, we treated 6 SIV-uninfected and 9 SIV-infected SMs with 2'-bromo-5'-deoxyuridine (BrdU) for 14 days and longitudinally assessed CD4+ T-cell subset turnover by polychromatic flow cytometry. We observed that, in SIV-infected SMs, turnover of CD4+ T-cell naïve and central, transitional, and effector memory subsets is comparable to that in uninfected animals. Comparable turnover of CD4+ T-cell subsets irrespective of SIV-infection status likely contributes to the lack of aberrant immune activation and disease progression observed after infection in non-progressive hosts.
记忆性CD4+ T细胞的异常更新是获得性免疫缺陷综合征(AIDS)进展的核心。了解天然宿主感染猿猴免疫缺陷病毒(SIV)期间CD4+亚群更新与免疫稳态之间的关系,可能有助于深入了解免疫调节机制,这些机制可作为治疗人类免疫缺陷病毒(HIV)感染者的干预模型。乌白眉猴(SMs)与SIV共同自然进化,以避免AIDS进展,同时维持外周CD4+ T细胞计数健康,因此代表了一种可阐明AIDS进展治疗干预措施的模型。为了评估非进展性宿主感染SIV期间CD4+亚群更新与免疫稳态之间的关系,我们用2'-溴-5'-脱氧尿苷(BrdU)处理了6只未感染SIV和9只感染SIV的SMs,为期14天,并通过多色流式细胞术纵向评估CD4+ T细胞亚群更新。我们观察到,在感染SIV的SMs中,CD4+ T细胞初始、中枢、过渡和效应记忆亚群的更新与未感染动物相当。无论SIV感染状态如何,CD4+ T细胞亚群的更新相当,这可能是导致非进展性宿主感染后未观察到异常免疫激活和疾病进展的原因。