Department of Medicine, UCLA AIDS Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
PLoS One. 2011 Jan 26;6(1):e16459. doi: 10.1371/journal.pone.0016459.
HIV-1-infected adults over the age of 50 years progress to AIDS more rapidly than adults in their twenties or thirties. In addition, HIV-1-infected individuals receiving antiretroviral therapy (ART) present with clinical diseases, such as various cancers and liver disease, more commonly seen in older uninfected adults. These observations suggest that HIV-1 infection in older persons can have detrimental immunological effects that are not completely reversed by ART. As naïve T-cells are critically important in responses to neoantigens, we first analyzed two subsets (CD45RA(+)CD31(+) and CD45RA(+)CD31(-)) within the naïve CD4(+) T-cell compartment in young (20-32 years old) and older (39-58 years old), ART-naïve, HIV-1 seropositive individuals within 1-3 years of infection and in age-matched seronegative controls. HIV-1 infection in the young cohort was associated with lower absolute numbers of, and shorter telomere lengths within, both CD45RA(+)CD31(+)CD4(+) and CD45RA(+)CD31(-)CD4(+) T-cell subsets in comparison to age-matched seronegative controls, changes that resembled seronegative individuals who were decades older. Longitudinal analysis provided evidence of thymic emigration and reconstitution of CD45RA(+)CD31(+)CD4(+) T-cells two years post-ART, but minimal reconstitution of the CD45RA(+)CD31(-)CD4(+) subset, which could impair de novo immune responses. For both ART-naïve and ART-treated HIV-1-infected adults, a renewable pool of thymic emigrants is necessary to maintain CD4(+) T-cell homeostasis. Overall, these results offer a partial explanation both for the faster disease progression of older adults and the observation that viral responders to ART present with clinical diseases associated with older adults.
HIV-1 感染的 50 岁以上成年人比 20 至 30 岁的成年人更快进展为艾滋病。此外，接受抗逆转录病毒治疗 (ART) 的 HIV-1 感染者更常见出现各种癌症和肝病等临床疾病，这些疾病在未感染的老年成年人中更为常见。这些观察结果表明，HIV-1 感染老年人可能会产生不完全通过 ART 逆转的有害免疫效应。由于幼稚 T 细胞在对新抗原的反应中至关重要，我们首先分析了年轻（20-32 岁）和老年（39-58 岁）、未经 ART 治疗、HIV-1 血清阳性、感染后 1-3 年内的幼稚 CD4+T 细胞区室中的两个亚群（CD45RA+CD31+和 CD45RA+CD31-），并与年龄匹配的血清阴性对照进行比较。与年龄匹配的血清阴性对照相比，年轻队列中的 HIV-1 感染与 CD45RA+CD31+CD4+和 CD45RA+CD31-CD4+T 细胞亚群中绝对数量较低且端粒较短相关，这些变化类似于年龄较大的血清阴性个体。纵向分析提供了证据表明，在 ART 治疗后两年，CD45RA+CD31+CD4+T 细胞有胸腺迁出和重建，但 CD45RA+CD31-CD4+亚群的重建很少，这可能会损害新的免疫反应。对于未经 ART 治疗和接受 ART 治疗的 HIV-1 感染者，需要有可再生的胸腺迁出细胞池来维持 CD4+T 细胞的稳态。总体而言，这些结果部分解释了为什么老年人疾病进展更快，以及为什么对 ART 有病毒反应的成年人会出现与老年人相关的临床疾病。
