AUTHOR=Rodriguez Stéphane , Alizadeh Mehdi , Lamaison Claire , Saintamand Alexis , Monvoisin Céline , Jean Rachel , Deleurme Laurent , Martin-Subero Jose Ignacio , Pangault Céline , Cogné Michel , Amé-Thomas Patricia , Tarte Karin 

TITLE=Follicular lymphoma regulatory T-cell origin and function

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1391404

DOI=10.3389/fimmu.2024.1391404

ISSN=1664-3224

ABSTRACT=Follicular Lymphoma (FL) results from the malignant transformation of germinal center (GC) B cells. FL B cells display recurrent and diverse genetic alterations, some of them favoring their direct interaction with their cell microenvironment, including follicular helper T cells (Tfh). Although FL-Tfh key role is well-documented, the impact of their regulatory counterpart, the follicular regulatory T cell (Tfr) compartment, is still sparse. The aim of this study was to characterize FL-Tfr phenotype, gene expression profile, origin, and functionality. CD4 + CXCR5 + CD25 hi ICOS + FL-Tfr displayed a regulatory program that is close to classical regulatory T cell (Treg) program, at the transcriptomic and methylome levels. Accordingly, Tfr imprinting stigmata were found on FL-Tfh and FL-B cells, compared to their physiological counterparts. In addition, FL-Tfr co-culture with autologous FL-Tfh or cytotoxic FL-CD8 + T cells inhibited their proliferation in vitro. Finally, although FL-Tfr shared many characteristics with Treg, TCR sequencing analyses demonstrated that part of them derived from precursors shared with FL-Tfh. Altogether, these findings uncover the role and origin of a Tfr subset in FL niche and may be useful for lymphomagenesis knowledge and therapeutic management.