title: CXCR5+CD4+ follicular helper T cells accumulate in resting human lymph nodes and have superior B cell helper activity.
abstract: Although many relevant immune reactions are initiated in the lymph nodes, this compartment has not been systematically studied in humans. Analyses have been performed on immune cells derived from tonsils, but as this tissue is most often inflamed, generalization of these data is difficult. Here, we analyzed the phenotype and function of the human CD4(+) T-cell subsets and lineages in paired resting lymph node and peripheral blood samples. Naive, central memory cells and effector memory cells as well as Th1, Th2, Th17 and Treg cells were equally represented in both compartments. On the other hand, cytotoxic CD4(+) T cells were strikingly absent in the lymph nodes. CXCR5(+)CD4(+) T cells, representing putative follicular Th (Tfh) cells were over-represented in lymph nodes and expressed higher levels of Tfh markers than their peripheral blood counterparts. Compared with the circulating pool, lymph-node-derived CXCR5(+)CD4(+) T cells were superior in providing help to B cells. Thus, functionally competent Tfh cells accumulate in resting human lymph nodes, providing a swift induction of naive and memory antibody responses upon antigenic challenge.
authors.affiliation: Department of Experimental Immunology.
authors.forename: Simone H C
authors.initials: SH
authors.lastname: Havenith
authors.forename: Ester B M
authors.initials: EB
authors.lastname: Remmerswaal
authors.forename: Mirza M
authors.initials: MM
authors.lastname: Idu
authors.forename: Karlijn A M I
authors.initials: KA
authors.lastname: van Donselaar-van der Pant
authors.forename: Nelly
authors.initials: N
authors.lastname: van der Bom
authors.forename: Fréderike J
authors.initials: FJ
authors.lastname: Bemelman
authors.forename: Ester M M
authors.initials: EM
authors.lastname: van Leeuwen
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: ten Berge
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D001773:Blood Cells / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D016030:Kidney Transplantation; D008198:Lymph Nodes / Q000276:immunology*; D008875:Middle Aged; D054380:Receptors, CXCR5 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology; D055815:Young Adult
chemical_list: D015704:CD4 Antigens; C095085:CXCR5 protein, human; D054380:Receptors, CXCR5
keywords: B-cell help; CD4+ T cells; follicular T helper cells; human lymph nodes