The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood

PT Sage, LM Francisco, CV Carman, AH Sharpe - Nature immunology, 2013 - nature.com
PT Sage, LM Francisco, CV Carman, AH Sharpe
Nature immunology, 2013nature.com
Abstract CD4+ CXCR5+ Foxp3+ follicular regulatory T cells (TFR cells) inhibit humoral
immunity mediated by CD4+ CXCR5+ Foxp3− follicular helper T cells (TFH cells). Although
the inhibitory receptor PD-1 is expressed by both cell types, its role in the differentiation of
tFR cells is unknown. Here we found that mice deficient in PD-1 and its ligand PD-L1 had a
greater abundance of tFR cells in the lymph nodes and that those tFR cells had enhanced
suppressive ability. We also found substantial populations of tFR cells in mouse blood and …
Abstract
CD4+CXCR5+Foxp3+ follicular regulatory T cells (TFR cells) inhibit humoral immunity mediated by CD4+CXCR5+Foxp3 follicular helper T cells (TFH cells). Although the inhibitory receptor PD-1 is expressed by both cell types, its role in the differentiation of TFR cells is unknown. Here we found that mice deficient in PD-1 and its ligand PD-L1 had a greater abundance of TFR cells in the lymph nodes and that those TFR cells had enhanced suppressive ability. We also found substantial populations of TFR cells in mouse blood and demonstrated that TFR cells in the blood homed to lymph nodes and potently inhibited TFH cells in vivo. TFR cells in the blood required signaling via the costimulatory receptors CD28 and ICOS but were inhibited by PD-1 and PD-L1. Our findings demonstrate mechanisms by which the PD-1 pathway regulates antibody production and help reconcile inconsistencies surrounding the role of this pathway in humoral immunity.
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