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

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 ^dim CXCR5 ⁺ 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 ^hi CXCR5 ^hi CD4 ⁺ mature follicular helper T cells, PD1 ^dim CXCR5 ⁺ 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 ^dim CD4 ⁺ T cells may contribute to the FL IL-4 rich environment, thus providing new insights in FL lymphomagenesis.
(Copyright © 2020 Misiak, Jean, Rodriguez, Deleurme, Lamy, Tarte and Amé-Thomas.)