Preprint Article Version 1 This version is not peer-reviewed

Follicular Immune Landscaping Reveals a Distinct Profile of FOXP3hi CD4+ T Cells in Treated Compared to Untreated HIV

Version 1 : Received: 15 July 2024 / Approved: 15 July 2024 / Online: 16 July 2024 (03:17:26 CEST)

How to cite: Georgakis, S.; Orfanakis, M.; Brenna, C.; Burgermeister, S.; Del Rio Estrada, P. M.; Navarro, M. G.; Torres-Ruiz, F.; Reyes Terán, G.; Avila Rios, S.; Luna-Villalobos, Y. A.; Chen, O. Y.; Pantaleo, G.; Koup, R. A.; Petrovas, C. Follicular Immune Landscaping Reveals a Distinct Profile of FOXP3hi CD4+ T Cells in Treated Compared to Untreated HIV. Preprints 2024, 2024071185. https://doi.org/10.20944/preprints202407.1185.v1 Georgakis, S.; Orfanakis, M.; Brenna, C.; Burgermeister, S.; Del Rio Estrada, P. M.; Navarro, M. G.; Torres-Ruiz, F.; Reyes Terán, G.; Avila Rios, S.; Luna-Villalobos, Y. A.; Chen, O. Y.; Pantaleo, G.; Koup, R. A.; Petrovas, C. Follicular Immune Landscaping Reveals a Distinct Profile of FOXP3hi CD4+ T Cells in Treated Compared to Untreated HIV. Preprints 2024, 2024071185. https://doi.org/10.20944/preprints202407.1185.v1

Abstract

Follicular helper CD4+ T cells (TFH) are a major cellular pool for the maintenance of 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 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 TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distribution of PD1hi TFH cells. The significantly accumulated follicular, compared to extrafollicular, FOXP3hi CD4+ T cells found in the low-TFH cART-HIV group were characterized by a less scattered in situ distribution and strongly correlated with the cell density of CD8+ T cells in this group. An inverse correlation between plasma viral load and LN GrzBhiCD8+ T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hi CD4+ T cells could be negative regulators of TFH cell prevalence in cART-HIV.

Keywords

HIV; germinal center; imaging; CD4 T cells

Subject

Biology and Life Sciences, Immunology and Microbiology

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