Laboratory of Vaccinology/Biobanking, The Chantal Biya International Reference Center (CIRCB) for Research on the Prevention and Management of HIV/AIDS, P.O. Box: 3077, Messa Yaoundé, Cameroon.
Department of Animal Biology and Physiology, University of Yaoundé I, Yaoundé, Cameroon.
BMC Immunol. 2024 Oct 14;25(1):68. doi: 10.1186/s12865-024-00654-8.
We previously demonstrated that the overall number of regulatory T (Treg) cells decrease proportionately with helper CD4 T cells and their frequencies increase in antiretroviral therapy (ART)-naive human immunodeficiency virus type-1 (HIV-1) infected individuals. The question now is whether the discrepancies in Treg cell numbers and frequencies are synonymous to an impairment of their functions. To address this, we purified Treg cells and assessed their ability to modulate autologous monocytes functions. We observed that Treg cells were able to down modulate autologous monocytes activation as well as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) production during stimulation with polyinosinic-polycytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose (poly-ICLC). This activity of Treg cells has been shown to be influenced by immunocompetence including but not limited to helper CD4 T cell counts, in individuals with HIV-1 infection. Compared to immunosuppressed participants (CD4 < 500 cells/µL), immunocompetent participants (CD4 ≥ 500 cells/µL) showed significantly higher levels of transforming growth factor beta (TGF-β) and IL-10 (p < 0.001 and p < 0.05, respectively), key cytokines used by Treg cells to exert their immunosuppressive functions. Our findings suggest the contribution of both TGF-β and IL-10 in the suppressive activity of Treg cells.
我们之前的研究表明,调节性 T(Treg)细胞的总数与辅助性 CD4 T 细胞成比例减少,并且在接受抗逆转录病毒治疗(ART)的人类免疫缺陷病毒 1(HIV-1)感染个体中其频率增加。现在的问题是 Treg 细胞数量和频率的差异是否与其功能障碍有关。为了解决这个问题,我们纯化了 Treg 细胞,并评估了它们调节自体单核细胞功能的能力。我们观察到 Treg 细胞能够下调自体单核细胞的激活以及白细胞介素 6(IL-6)和肿瘤坏死因子-α(TNF-α)的产生,当用多聚肌苷酸-多聚胞苷酸稳定的多聚赖氨酸和羧甲基纤维素(poly-ICLC)刺激时。已经表明,Treg 细胞的这种活性受到免疫能力的影响,包括但不限于 HIV-1 感染个体中的辅助性 CD4 T 细胞计数。与免疫抑制参与者(CD4 <500 个细胞/µL)相比,免疫能力参与者(CD4 ≥500 个细胞/µL)表现出显著更高水平的转化生长因子β(TGF-β)和白细胞介素 10(p <0.001 和 p <0.05,分别),这是 Treg 细胞发挥其免疫抑制功能所使用的关键细胞因子。我们的发现表明 TGF-β和 IL-10 都有助于 Treg 细胞的抑制活性。