Laboratory of Immunoregulation.
NIAID Collaborative Bioinformatics Resource (NCBR), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
AIDS. 2022 Nov 15;36(14):1935-1940. doi: 10.1097/QAD.0000000000003331. Epub 2022 Jul 16.
HIV induces immunologic dysfunction in T cells of infected individuals. However, the impact of aging on T cell phenotypes in HIV-infected individuals receiving antiretroviral therapy (ART) has not been fully delineated. We evaluated the relationship between aging and the expression of immune activation and exhaustion markers on CD8 + T cells of age-matched HIV-infected and -uninfected male participants.
Levels of immune activation and exhaustion markers on peripheral blood CD8 + T cells of HIV-infected and -uninfected participants were examined.
110 HIV-infected aviremic male participants receiving ART and 146 HIV-uninfected male participants were studied. The levels of TIGIT, PD-1, CD38, and CD226 on CD8 + T cells of the study participants were determined by flow cytometry.
The level of TIGIT on CD8 + T cells was higher in aviremic HIV-infected compared to uninfected participants ( P < 0.0001). In contrast, no significant differences were found in the levels of PD-1 and CD38 on CD8 + T cells between the two groups. Statistically significant correlations were observed between age and the levels of TIGIT + and CD38 + CD8 + T cells in both groups; however, no correlation was found between age and the level of PD-1 + CD8 + T cells in HIV-infected participants. Age-stratification of HIV-infected and -uninfected groups did not show any significant differences in the level of PD-1 expression on CD8 + T cells.
The findings of our study highlight the role of aging in the expression of immune markers on CD8 + T cells and have important implications for therapies that target immune checkpoints in HIV-infected individuals.
HIV 可诱导感染个体的 T 细胞免疫功能障碍。然而,在接受抗逆转录病毒疗法(ART)的 HIV 感染者中,衰老对 T 细胞表型的影响尚未完全阐明。我们评估了年龄与 HIV 感染和未感染男性参与者外周血 CD8+T 细胞上免疫激活和耗竭标志物表达之间的关系。
检查了 HIV 感染和未感染参与者外周血 CD8+T 细胞上免疫激活和耗竭标志物的水平。
研究了 110 名接受 ART 的 HIV 感染且病毒载量抑制的男性参与者和 146 名 HIV 未感染的男性参与者。通过流式细胞术测定研究参与者 CD8+T 细胞上 TIGIT、PD-1、CD38 和 CD226 的水平。
与未感染的参与者相比,病毒载量抑制的 HIV 感染者的 CD8+T 细胞上 TIGIT 的水平更高(P<0.0001)。相比之下,两组间 CD8+T 细胞上 PD-1 和 CD38 的水平没有差异。在两组中,年龄与 TIGIT+和 CD38+CD8+T 细胞的水平之间均观察到统计学显著的相关性;然而,在 HIV 感染者中,年龄与 PD-1+CD8+T 细胞的水平之间未发现相关性。对 HIV 感染和未感染组进行年龄分层,CD8+T 细胞上 PD-1 表达的水平没有差异。
我们的研究结果强调了衰老对 CD8+T 细胞上免疫标志物表达的作用,并对针对 HIV 感染者免疫检查点的治疗具有重要意义。