Laboratorio Inmuno-Biología Molecular (LIBM), Immunology Section, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain.
PLoS One. 2020 Mar 18;15(3):e0230339. doi: 10.1371/journal.pone.0230339. eCollection 2020.
People living with HIV-1 experience an accelerated aging due to the persistent and chronic activation of the immune system. This phenomenon conduces to immune exhaustion and precipitate immunosenescence. In general, frailty is defined as a syndrome of physiological degeneration in the elderly. Circulating naïve and memory T cells were studied by flow cytometry in non-frail and frail HIV-1-infected groups. Thymopoiesis, cell activation, senescence and cell proliferation were analyzed by CD31, HLA-DR/CD38, CD28/CD57 and Ki-67 expression, respectively. Plasma levels of sCD14 and MDA were measured by ELISA. Frail infected individuals showed a reduced number of memory T cells, both CD4+ and CD8+ populations. Activated CD3+CD4+HLA-DR+ T cells were lower in frail individuals, and directly correlated with CD3+CD8+HLA-DR+ and CD8M cells. Senescent CD8+CD28-CD57+ cells were reduced in frail HIV-1 infected individuals and inversely correlated with CD8RTE, CD8N and CD3+CD4+HLA-DR+. Higher plasma levels of sCD14 and MDA were found in HIV-1 infected frail individuals. Our data show association among frailty, markers of immune activation and oxidative stress. Understanding the immune mechanisms underlying frailty status in HIV-1 population is of high relevance not only for the prediction of continuing longevity but also for the identification of potential strategies for the elderly.
HIV-1 感染者会经历免疫系统的持续和慢性激活所导致的加速衰老。这种现象导致免疫衰竭和免疫衰老。一般来说,虚弱被定义为老年人的生理衰退综合征。通过流式细胞术研究了非虚弱和虚弱的 HIV-1 感染者群体中的循环幼稚和记忆 T 细胞。通过 CD31、HLA-DR/CD38、CD28/CD57 和 Ki-67 的表达分别分析了胸腺生成、细胞激活、衰老和细胞增殖。通过 ELISA 测量了 sCD14 和 MDA 的血浆水平。虚弱的感染者表现出记忆 T 细胞数量减少,包括 CD4+和 CD8+群体。虚弱个体中激活的 CD3+CD4+HLA-DR+T 细胞减少,并且与 CD3+CD8+HLA-DR+和 CD8M 细胞直接相关。衰老的 CD8+CD28-CD57+细胞在虚弱的 HIV-1 感染者中减少,并且与 CD8RTE、CD8N 和 CD3+CD4+HLA-DR+呈负相关。在 HIV-1 感染的虚弱个体中发现了更高水平的 sCD14 和 MDA。我们的数据表明,虚弱、免疫激活标志物和氧化应激之间存在关联。了解 HIV-1 人群中虚弱状态的免疫机制不仅对于预测持续长寿具有重要意义,而且对于确定老年人的潜在策略也具有重要意义。