title: Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion.
abstract: Although a fraction of human blood memory CD4(+) T cells expresses chemokine (C-X-C motif) receptor 5 (CXCR5), their relationship to T follicular helper (Tfh) cells is not well established. Here we show that human blood CXCR5(+)CD4(+) T cells share functional properties with Tfh cells and appear to represent their circulating memory compartment. Blood CXCR5(+)CD4(+) T cells comprised three subsets: T helper 1 (Th1), Th2, and Th17 cells. Th2 and Th17 cells within CXCR5(+), but not within CXCR5(-), compartment efficiently induced naive B cells to produce immunoglobulins via interleukin-21 (IL-21). In contrast, Th1 cells from both CXCR5(+) and CXCR5(-) compartments lacked the capacity to help B cells. Patients with juvenile dermatomyositis, a systemic autoimmune disease, displayed a profound skewing of blood CXCR5(+) Th cell subsets toward Th2 and Th17 cells. Importantly, the skewing of subsets correlated with disease activity and frequency of blood plasmablasts. Collectively, our study suggests that an altered balance of Tfh cell subsets contributes to human autoimmunity.
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204, USA.
authors.forename: Rimpei
authors.initials: R
authors.lastname: Morita
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schmitt
authors.forename: Salah-Eddine
authors.initials: SE
authors.lastname: Bentebibel
authors.forename: Rajaram
authors.initials: R
authors.lastname: Ranganathan
authors.forename: Laure
authors.initials: L
authors.lastname: Bourdery
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.forename: Emile
authors.initials: E
authors.lastname: Foucat
authors.forename: Melissa
authors.initials: M
authors.lastname: Dullaers
authors.forename: SangKon
authors.initials: S
authors.lastname: Oh
authors.forename: Natalie
authors.initials: N
authors.lastname: Sabzghabaei
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Lavecchio
authors.forename: Marilynn
authors.initials: M
authors.lastname: Punaro
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015704:CD4 Antigens / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D003882:Dermatomyositis / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007378:Interleukins / Q000378:metabolism; D008297:Male; D019899:Paracrine Communication; D054380:Receptors, CXCR5 / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058408:Th1-Th2 Balance; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000098546:Interleukin-21
chemical_list: D015704:CD4 Antigens; C095085:CXCR5 protein, human; D007378:Interleukins; D054380:Receptors, CXCR5; D000098546:Interleukin-21