Frontiers in Immunology (May 2024)

Follicular lymphoma regulatory T-cell origin and function

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

DOI
https://doi.org/10.3389/fimmu.2024.1391404
Journal volume & issue
Vol. 15

Abstract

Read online

IntroductionFollicular 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.MethodsThe aim of this study was to characterize FL-Tfr phenotype by cytometry, gene expression profile, FL-Tfr origin by transcriptomic analysis, and functionality by in vitro assays.ResultsCD4+CXCR5+CD25hiICOS+ 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. DiscussionAltogether, these findings uncover the role and origin of a Tfr subset in FL niche and may be useful for lymphomagenesis knowledge and therapeutic management.

Keywords