AUTHOR=Misiak Jan , Jean Rachel , Rodriguez Stéphane , Deleurme Laurent , Lamy Thierry , Tarte Karin , Amé-Thomas Patricia 

TITLE=Human Lymphoid Stromal Cells Contribute to Polarization of Follicular T Cells Into IL-4 Secreting Cells

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.559866

DOI=10.3389/fimmu.2020.559866

ISSN=1664-3224

ABSTRACT=<p>Fibroblastic reticular cells (FRCs) are the specialized lymphoid stromal cells initially identified as triggering T-cell recruitment and dynamic motion in secondary lymphoid organs. Interestingly, FRCs also display antigen presentation capacities and support lymphocyte survival. CXCR5<sup>+</sup>CD4<sup>+</sup> follicular T cells are important players of B-cell maturation and antibody response. Our study reported that <italic>in vitro</italic>-differentiated FRC-like cells enhanced the growth of the whole CXCR5<sup>+</sup>CD4<sup>+</sup> T-cell compartment, while enhancing IL-4 secretion specifically by the PD1<sup>dim</sup>CXCR5<sup>+</sup>CD4<sup>+</sup> cell subset, in a Notch- and ICAM1/LFA1-dependent manner. In addition, we revealed that in follicular lymphoma (FL) tissues, previously identified as enriched for PD1<sup>hi</sup>CXCR5<sup>hi</sup>CD4<sup>+</sup> mature follicular helper T cells, PD1<sup>dim</sup>CXCR5<sup>+</sup>CD4<sup>+</sup> T cells displayed an enrichment for Notch and integrin gene signatures, and a Notch and ICAM-1-dependent overexpression of IL-4 compared to their non-malignant counterparts. These findings suggest that the crosstalk between FRCs and CXCR5<sup>+</sup>PD1<sup>dim</sup>CD4<sup>+</sup> T cells may contribute to the FL IL-4 rich environment, thus providing new insights in FL lymphomagenesis.</p>