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

Abstract

CXCR5+CD4+ T cells localized in secondary lymphoid organs are important players of B-cell maturation and antibody responses. Fibroblastic reticular cells (FRCs) are specialized stromal cells found in close contact with CD4+ T cells allowing their recruitment and dynamic motion. Interestingly, several studies demonstrate survival effect on lymphocytes and antigen-presenting cell properties of stromal cells, hypothesizing stronger interactions between FRCs and CD4+ T cells than previously assumed. This study reports that in vitro-differentiated FRC-like cells enhance CXCR5+CD4+ T cell growth, and induce IL-4 over-secretion by PD1dimCXCR5+CD4+ T cells in a Notch- and ICAM1/LFA1-dependent manner. Of note, we revealed that PD1dimCXCR5+CD4+ T cells from follicular lymphoma lymph nodes display enriched Notch and integrin gene signatures, as well as an overexpression of IL-4, compared to non-malignant counterparts. These findings hypothesize that FRC - CXCR5+PD1dimCD4+ T cell interactions may participate to FL IL-4 rich environment and therefore provide new insights on FL lymphomagenesis.