Georgakis Spiros, Orfanakis Michail, Brenna Cloe, Burgermeister Simon, Del Rio Estrada Perla M, González-Navarro Mauricio, Torres-Ruiz Fernanda, Reyes-Terán Gustavo, Avila-Rios Santiago, Luna-Villalobos Yara Andrea, Chén Oliver Y, Pantaleo Giuseppe, Koup Richard A, Petrovas Constantinos
Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital, University of Lausanne, Rue du Bugnon 25, CH-1011 Lausanne, Switzerland.
Centro de Investigacion en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas", Mexico City 14080, Mexico.
Vaccines (Basel). 2024 Aug 12;12(8):912. doi: 10.3390/vaccines12080912.
Follicular helper CD4 T cells (T) are a major cellular pool for the maintenance of the HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with the relevant computational tools, to investigate F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral-treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls. Lymph nodes (LNs) from viremic and cART PLWH could be further grouped based on their T cell densities in high-T and low-T subgroups. These subgroups were also characterized by different in situ distributions of PD1 T cells. Furthermore, a significant accumulation of follicular FOXP3CD4 T cells, which were characterized by a low scattering in situ distribution profile and strongly correlated with the cell density of CD8 T cells, was found in the cART-HIV low-TFH group. An inverse correlation between plasma viral load and LN GrzBCD8 T and CD16CD15 cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3CD4 T cells could be negative regulators of T cell prevalence in cART-HIV.
滤泡辅助性CD4 T细胞（Tfh）是维持HIV病毒库的主要细胞池。因此，描绘滤泡（F）/生发中心（GC）免疫格局将显著推进我们对HIV发病机制的理解。我们应用多重共聚焦成像技术，结合相关计算工具，研究病毒血症（vir-HIV）、接受抗逆转录病毒治疗（cART HIV）的HIV感染者（PLWH）的F/GC原位免疫动力学，并将其与反应性、未感染的对照组进行比较。病毒血症和cART PLWH的淋巴结（LNs）可根据其T细胞密度进一步分为高T和低T亚组。这些亚组还具有不同的PD1 T细胞原位分布特征。此外，在cART-HIV低Tfh组中发现滤泡性FOXP3+CD4 T细胞显著积聚，其特征是原位分布散射低，且与CD8 T细胞的细胞密度密切相关。发现血浆病毒载量与LN GrzB+CD8 T细胞和CD16+CD15细胞呈负相关。我们的数据揭示了HIV感染中复杂的GC免疫格局，并表明滤泡性FOXP3+CD4 T细胞可能是cART-HIV中T细胞流行率的负调节因子。
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