# Follicular Immune Landscaping Reveals a Distinct Profile of FOXP3hiCD4hi T Cells in Treated Compared to Untreated HIV

## TL;DR

This study explores immune cell patterns in lymph nodes of HIV patients and finds a unique profile of FOXP3hiCD4hi T cells in those receiving treatment.

## Contribution

The study identifies a distinct accumulation of FOXP3hiCD4hi T cells in treated HIV patients, suggesting a regulatory role in follicular immune dynamics.

## Key findings

- cART-HIV patients show increased follicular FOXP3hiCD4hi T cells correlated with CD8hi T cell density.
- Low-TFH cART-HIV subgroup has unique PD1hi TFH distribution and FOXP3hiCD4hi T cell accumulation.
- Plasma viral load inversely correlates with GrzBhiCD8hi and CD16hiCD15lo cell densities in lymph nodes.

## Abstract

Follicular helper CD4hi T cells (TFH) 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 TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distributions of PD1hi TFH cells. Furthermore, a significant accumulation of follicular FOXP3hiCD4hi T cells, which were characterized by a low scattering in situ distribution profile and strongly correlated with the cell density of CD8hi T cells, was found in the cART-HIV low-TFH group. An inverse correlation between plasma viral load and LN GrzBhiCD8hi T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hiCD4hi T cells could be negative regulators of TFH cell prevalence in cART-HIV.