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

Abstract

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⁺CD4⁺ follicular T cells are important players of B-cell maturation and antibody response. Our study reported that in vitro-differentiated FRC-like cells enhanced the growth of the whole CXCR5⁺CD4⁺ T-cell compartment, while enhancing IL-4 secretion specifically by the PD1^dimCXCR5⁺CD4⁺ 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^hiCXCR5^hiCD4⁺ mature follicular helper T cells, PD1^dimCXCR5⁺CD4⁺ 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⁺PD1^dimCD4⁺ T cells may contribute to the FL IL-4 rich environment, thus providing new insights in FL lymphomagenesis.

Keywords: IL-4; T follicular helper cells; fibroblastic reticular cells; follicular T cells; follicular lymphoma.