title: Circulating precursor CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure.
abstract: Follicular B helper T (Tfh) cells support high affinity and long-term antibody responses. Here we found that within circulating CXCR5⁺ CD4⁺ T cells in humans and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype, whereas CCR7(hi)PD-1(lo) cells have a resting phenotype. The circulating CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases. Thus the CCR7(lo)PD-1(hi) subset provides a biomarker to monitor protective antibody responses during infection or vaccination and pathogenic antibody responses in autoimmune diseases. Differentiation of both CCR7(hi)PD-1(lo) and CCR7(lo)PD-1(hi) subsets required ICOS and BCL6, but not SAP, suggesting that circulating CXCR5⁺ helper T cells are primarily generated before germinal centers. Upon antigen reencounter, CCR7(lo)PD-1(hi) CXCR5⁺ precursors rapidly differentiate into mature Tfh cells to promote antibody responses. Therefore, circulating CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells are generated during active Tfh differentiation and represent a new mechanism of immunological early memory.
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.forename: Louis M
authors.initials: LM
authors.lastname: Tsai
authors.forename: Yew Ann
authors.initials: YA
authors.lastname: Leong
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.forename: Cindy S
authors.initials: CS
authors.lastname: Ma
authors.forename: Nina
authors.initials: N
authors.lastname: Chevalier
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Sun
authors.forename: Kirsten
authors.initials: K
authors.lastname: Vandenberg
authors.forename: Steve
authors.initials: S
authors.lastname: Rockman
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Changqi
authors.initials: C
authors.lastname: Wang
authors.forename: Alexander
authors.initials: A
authors.lastname: Karnowski
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.forename: Joanna R
authors.initials: JR
authors.lastname: Ghali
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Cook
authors.forename: D Sean
authors.initials: DS
authors.lastname: Riminton
authors.forename: André
authors.initials: A
authors.lastname: Veillette
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Schwartzberg
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
authors.forename: Robert
authors.initials: R
authors.lastname: Brink
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Tangye
authors.forename: Carola G
authors.initials: CG
authors.lastname: Vinuesa
authors.forename: Charles R
authors.initials: CR
authors.lastname: Mackay
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Li
authors.forename: Di
authors.initials: D
authors.lastname: Yu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D018858:Germinal Center / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D056724:Immunity, Humoral; D007156:Immunologic Memory; D016130:Immunophenotyping; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology*; D051560:Proto-Oncogene Proteins c-bcl-6; D054387:Receptors, CXCR / Q000235:genetics / Q000276:immunology*; D054380:Receptors, CXCR5 / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: C501896:ACKR3 protein, human; D000906:Antibodies; D000941:Antigens; C084103:BCL6 protein, human; C095085:CXCR5 protein, human; D004268:DNA-Binding Proteins; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D051560:Proto-Oncogene Proteins c-bcl-6; D054387:Receptors, CXCR; D054380:Receptors, CXCR5