在慢性感染 HIV-1 的莫桑比克个体中，表达 Helios 的调节性 T 细胞与产生 IL-2 的 CD8 T 细胞减少和抗体多样性降低相关。
Helios expressing regulatory T cells are correlated with decreased IL-2 producing CD8 T cells and antibody diversity in Mozambican individuals living chronically with HIV-1.
机构信息
Instituto Nacional de Saúde, Distrito de Marracuene, Estrada Nacional N°1, Marracuene, Província de Maputo, Mozambique.
Institute of Tropical Medicine, Department of Biomedical Sciences, Antwerp, Belgium.
出版信息
BMC Immunol. 2022 Mar 14;23(1):12. doi: 10.1186/s12865-022-00487-3.
BACKGROUND
Human immunodeficiency virus type 1 (HIV-1) causes impairment of T and B cell responses, which begins during the acute phase of infection and is not completely restored by antiretroviral treatment. Regulatory T cell (Tregs) can improve overall disease outcome by controlling chronic inflammation but may also suppress beneficial HIV-1 specific immune responses. We aimed to analyze the profile of Tregs and their correlation with the status of T cells activation, the expression of IL-2 and IFNγ and the profile of HIV-1 specific antibodies response in Mozambican people living chronically with HIV-1 (PLWH-C).
RESULTS
In PLWH-C, the proportion of total Tregs was positively correlated with the proportion of IL-2CD4 T cells (r = 0.647; p = 0.032) and IL-2IFNγCD8 T cells (r = 0.551; p = 0.014), while the proportions of HeliosTregs correlated inversely with levels of IL-2CD8 T cells (r = - 0.541; p = 0.017). Overall, PLWH-C, with (82%) or without virologic suppression (64%), were seronegative for at least HIV-1 p31, gp160 or p24, and the breadth of antibody responses was positively correlated with proportions of CD38HLA-DRCD8 T cells (r = 0.620; p = 0.012), viral load (r = 0.452; p = 0.040) and inversely with absolute CD4 T cells count (r = - 0.481; p = 0.027). Analysis of all individuals living HIV-1 showed that the breadth of HIV-1 antibody responses was inversely correlated with the proportion of HeliosTregs (r = - 0.45; p = 0.02).
CONCLUSION
Among Mozambican people living with HIV-1, seronegativity to some HIV-1 proteins is common, particularly in virologically suppressed individuals. Furthermore, lower diversity of HIV-specific antibodies is correlated to lower immune activation, lower viral replication and higher CD4 counts, in PLWH-C. Elevation in the proportion of HeliosTregs is related to a reduction of CD8 T expressing intracellular IL-2, in PLWH-C, but may contribute to impairment of B cell function.
背景
人类免疫缺陷病毒 1 型（HIV-1）可导致 T 细胞和 B 细胞应答受损，这种损伤始于感染急性期，且并未完全通过抗逆转录病毒治疗得到恢复。调节性 T 细胞（Tregs）可通过控制慢性炎症来改善整体疾病预后，但也可能抑制有益的 HIV-1 特异性免疫应答。我们旨在分析莫桑比克慢性 HIV-1 感染者（PLWH-C）中 Tregs 的特征及其与 T 细胞活化状态、IL-2 和 IFNγ表达以及 HIV-1 特异性抗体反应特征的相关性。
结果
在 PLWH-C 中，总 Tregs 的比例与 IL-2CD4 T 细胞（r=0.647；p=0.032）和 IL-2IFNγCD8 T 细胞（r=0.551；p=0.014）的比例呈正相关，而 HeliosTregs 的比例与 IL-2CD8 T 细胞的水平呈负相关（r=-0.541；p=0.017）。总体而言，82%的 PLWH-C 患者（无论是否具有病毒学抑制）针对 HIV-1 p31、gp160 或 p24 至少呈血清阴性，且抗体反应的广度与 CD38HLA-DRCD8 T 细胞的比例（r=0.620；p=0.012）、病毒载量（r=0.452；p=0.040）呈正相关，与绝对 CD4 T 细胞计数呈负相关（r=-0.481；p=0.027）。对所有 HIV-1 感染者的分析表明，HIV-1 抗体反应的广度与 HeliosTregs 的比例呈负相关（r=-0.45；p=0.02）。
结论
在莫桑比克的 HIV-1 感染者中，针对某些 HIV-1 蛋白呈血清阴性较为常见，尤其是在病毒学抑制的个体中。此外，PLWH-C 中 HIV 特异性抗体的多样性较低与免疫激活程度较低、病毒复制较低和 CD4 计数较高相关。在 PLWH-C 中，HeliosTregs 比例的升高与 CD8 T 细胞内表达的 IL-2 减少有关，但可能导致 B 细胞功能受损。
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