Romero-Rodríguez Dámaris P, Romero-Rodríguez Jessica, Cervantes-Mejía Fernanda, Olvera-García Gustavo, Pérez-Patrigeon Santiago, Murakami-Ogasawara Akio, Romero-Mora Karla, Gómez-Palacio María, Reyes-Terán Gustavo, Jiang Wei, Espinosa Enrique
Flow Cytometry Core Facility, National Institute of Respiratory Diseases "Ismael Cosío Villegas," Mexico City, Mexico.
Laboratory of Integrative Immunology, National Institute of Respiratory Diseases, Mexico City, Mexico.
AIDS Res Hum Retroviruses. 2025 Jan;41(1):37-42. doi: 10.1089/aid.2024.0062. Epub 2024 Oct 28.
Central memory (T) cells are a subpopulation of CD4 T cells that sustain overall CD4 T cell counts in HIV infection. The mechanisms underlying their eventual demise, which leads to loss of CD4 T cell counts, are not known. To understand their proneness to death despite their increased movement to proliferation, we examined cell division together with possible cell accumulation in different phases of the cell cycle. Purified circulating T cells from untreated people living with HIV (PLWH) ( = 9) and healthy controls ( = 10) were stimulated using anti-CD3/CD28 agonistic antibodies plus IL-2 and cultured for 4 days. Cell viability, DNA content, proliferation, and cyclin A and cyclin B expression were measured. We found that PLWH T cells more frequently had a DNA content lower than G0/G1, compared with controls ( = .043). These cells accumulated with each division. The proportion of cells with sub-G0/G1 DNA content that were cycling (expressing cyclin A) was greater in the PLWH group ( = .003). The percentage of T cells expressing cyclin A+ among those in G0/G1 and was also greater in the PLWH group ( = .043), suggesting arrest before G2/M. While T cells from PLWH can proliferate, during this process some of them accumulate defects in DNA content that are incompatible with viability, suggesting that they could be intrinsically prone to cell cycle-dependent death. This provides a possible mechanism underlying the increased T cell turnover in HIV infection.
中枢记忆（T）细胞是CD4 T细胞的一个亚群，在HIV感染中维持总体CD4 T细胞计数。导致CD4 T细胞计数减少的这些细胞最终死亡的潜在机制尚不清楚。为了了解尽管它们向增殖方向的迁移增加但仍易于死亡的原因，我们研究了细胞分裂以及细胞周期不同阶段可能的细胞积累情况。使用抗CD3/CD28激动性抗体加白细胞介素-2刺激来自未接受治疗的HIV感染者（PLWH）（n = 9）和健康对照者（n = 10）的纯化循环T细胞，并培养4天。测量细胞活力、DNA含量、增殖以及细胞周期蛋白A和细胞周期蛋白B的表达。我们发现，与对照组相比，PLWH的T细胞DNA含量低于G0/G1的频率更高（P = 0.043）。这些细胞随着每次分裂而积累。在PLWH组中，处于亚G0/G1 DNA含量且正在循环（表达细胞周期蛋白A）的细胞比例更高（P = 0.003）。在G0/G1期表达细胞周期蛋白A+的T细胞百分比在PLWH组中也更高（P = 0.043），表明在G2/M期之前停滞。虽然来自PLWH的T细胞可以增殖，但在此过程中，其中一些细胞在DNA含量上积累了与活力不相容的缺陷，这表明它们可能内在地易于发生细胞周期依赖性死亡。这为HIV感染中T细胞周转率增加提供了一种可能的机制。
