Department of Immunobiology, The University of Arizona Health Sciences Center, Tucson, AZ, United States of America.
Department of Medicine, The University of Arizona Health Sciences Center, Tucson, AZ, United States of America.
PLoS One. 2020 Sep 17;15(9):e0236320. doi: 10.1371/journal.pone.0236320. eCollection 2020.
HIV-infected older individuals may have a diminished immune response because of exhaustion/immune aging of T-cells. Therefore, we have investigated HIV-specific CD4 and CD8 T-cell responses in 100 HIV-infected patients (HIV+) who have aged on long-term antiretroviral therapy (ART) and achieved controlled viremia (mostly undetectable viral load; 92 patients with <20 to <40 HIV RNA copies/mL and 8 <60 to <100) and improved CD4 T-cell counts. We show that the median frequencies of HIV-specific CD4+ and CD8+ IFN-γ T-cells were higher in HIV+ than uninfected individuals (HIV-), including increasing levels of IFN-γproduced by CD4+ T-cells and decreasing levels by CD8+ T-cells with increasing CD4 T-cell counts in HIV+. No correlation was found between T-cell responses and varying levels of undetectable viremia. HIV-specific TNF-α made by CD8+ T-cells was higher in HIV+ than HIV-, including decreasing levels with increasing CD4 T-cell counts in HIV+. Furthermore, the CD8+ T-cell mediators, CD107a and Granzyme-B, were higher in HIV+ than HIV-, and decreased with increasing CD4 T-cell counts in HIV+. Remarkably, HIV-specific CD8 T-cells produced decreasing levels of IFN-γwith increasing age of HIV+, including decreased levels of CD107a and Granzyme-B in older HIV+. However, HIV-specific CD8+ T-cells produced increasing levels of TNF-α with increasing age of the HIV+, suggesting continued inflammation. In conclusion, HIV+ with controlled viremia on long-term ART and with higher CD4 T-cell counts showed reduced HIV-specific CD8 T-cell responses as compared to those with lower CD4 T-cell counts, and older HIV+ exhibited decreasing levels of CD8 T-cell responses with increasing age.
HIV 感染的老年人可能由于 T 细胞耗竭/免疫衰老而产生减弱的免疫反应。因此，我们研究了 100 名长期接受抗逆转录病毒治疗（ART）且实现了病毒血症控制（大多数为不可检测的病毒载量；92 名患者的<20 至 <40 HIV RNA 拷贝/ml 和 8 名<60 至 <100）并改善了 CD4 T 细胞计数的 HIV 感染患者（HIV+）的 HIV 特异性 CD4 和 CD8 T 细胞反应。我们表明，与未感染个体（HIV-）相比，HIV+的 HIV 特异性 CD4+和 CD8+ IFN-γ T 细胞的中位数频率更高，包括随着 HIV+中 CD4+T 细胞产生 IFN-γ的水平增加和 CD8+T 细胞产生 IFN-γ的水平降低，随着 CD4 T 细胞计数的增加。未发现 T 细胞反应与不同水平的不可检测病毒血症之间存在相关性。与 HIV-相比，HIV+的 CD8+T 细胞产生的 HIV 特异性 TNF-α更高，包括随着 HIV+中 CD4 T 细胞计数的增加，TNF-α的水平降低。此外，与 HIV-相比，HIV+的 CD8+T 细胞介质 CD107a 和 Granzyme-B 更高，随着 HIV+中 CD4 T 细胞计数的增加而减少。值得注意的是，随着 HIV+年龄的增加，HIV 特异性 CD8 T 细胞产生的 IFN-γ水平降低，包括在老年 HIV+中 CD107a 和 Granzyme-B 水平降低。然而，随着 HIV+年龄的增加，HIV 特异性 CD8+T 细胞产生的 TNF-α水平增加，表明持续存在炎症。总之，与具有较低 CD4 T 细胞计数的患者相比，长期接受 ART 治疗且具有较高 CD4 T 细胞计数的 HIV+患者表现出降低的 HIV 特异性 CD8 T 细胞反应，而年龄较大的 HIV+患者随着年龄的增长表现出降低的 CD8 T 细胞反应。
