| First Author | Ritvo PG | Year | 2017 |
| Journal | Sci Immunol | Volume | 2 |
| Issue | 15 | PubMed ID | 28887367 |
| Mgi Jnum | J:259890 | Mgi Id | MGI:6141991 |
| Doi | 10.1126/sciimmunol.aan0368 | Citation | Ritvo PG, et al. (2017) Tfr cells lack IL-2Ralpha but express decoy IL-1R2 and IL-1Ra and suppress the IL-1-dependent activation of Tfh cells. Sci Immunol 2(15) |
| abstractText | Follicular regulatory T (Tfr) cells from lymph node germinal centers control follicular helper T (Tfh) cell-dependent B cell activation. These scarce cells, often described and purified as CD25(+) cells, are thought to be derived from thymic regulatory T (Treg) cells. However, we observed that mouse Tfr cells do not respond to interleukin-2 (IL-2), unlike Treg cells. Stringent immunophenotyping based on B cell lymphoma 6 (Bcl6), programmed cell death protein 1 (PD-1), and CXCR5 expression revealed that Tfr cells are actually CD25(-), in mice and humans. Moreover, Tfr cell characterization based only on CXCR5 and PD-1 high expression without excluding CD25(+) cells resulted in contamination with Treg cells. Transcriptome studies of CD4(+)CXCR5(+)PD-1(+)Bcl6(+)Foxp3(+)CD25(-) Tfr cells revealed that they express the IL-1 decoy receptor IL-1R2 and the IL-1 receptor antagonist IL-1Ra, whereas Tfh cells express the IL-1R1 agonist receptor. IL-1 treatment expanded Tfh cells in vivo and activated their production of IL-4 and IL-21 in vitro. Tfr cells suppressed the IL-1-induced activation of Tfh cells as efficiently as the IL-1 receptor antagonist Anakinra. Altogether, these results reveal an IL-1 axis in the Tfh cell control of B cell responses and an IL-2/IL-1 dichotomy for Treg cell control of effector T cells versus Tfr cell control of Tfh cells. |
