title: The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood.
abstract: CD4(+)CXCR5(+)Foxp3(+) follicular regulatory T cells (T(FR) cells) inhibit humoral immunity mediated by CD4(+)CXCR5(+)Foxp3(-) follicular helper T cells (T(FH) cells). Although the inhibitory receptor PD-1 is expressed by both cell types, its role in the differentiation of T(FR) cells is unknown. Here we found that mice deficient in PD-1 and its ligand PD-L1 had a greater abundance of T(FR) cells in the lymph nodes and that those T(FR) cells had enhanced suppressive ability. We also found substantial populations of T(FR) cells in mouse blood and demonstrated that T(FR) cells in the blood homed to lymph nodes and potently inhibited T(FH) cells in vivo. T(FR) 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.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Sage
authors.forename: Loise M
authors.initials: LM
authors.lastname: Francisco
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Carman
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D000917:Antibody Formation; D060890:B7-H1 Antigen / Q000097:blood / Q000235:genetics / Q000276:immunology; D018106:CD28 Antigens / Q000097:blood / Q000235:genetics / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D056724:Immunity, Humoral; D060889:Inducible T-Cell Co-Stimulator Protein / Q000097:blood / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008822:Mice, Transgenic; D061026:Programmed Cell Death 1 Receptor / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; D018106:CD28 Antigens; C498919:Cd274 protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor