title: IL-12 receptor β1 deficiency alters in vivo T follicular helper cell response in humans.
abstract: Antibody responses represent a key immune protection mechanism. T follicular helper (Tfh) cells are the major CD4(+) T-cell subset that provides help to B cells to generate an antibody response. Tfh cells together with B cells form germinal centers (GCs), the site where high-affinity B cells are selected and differentiate into either memory B cells or long-lived plasma cells. We show here that interleukin-12 receptor β1 (IL-12Rβ1)-mediated signaling is important for in vivo Tfh response in humans. Although not prone to B cell-deficient-associated infections, subjects lacking functional IL-12Rβ1, a receptor for IL-12 and IL-23, displayed substantially less circulating memory Tfh and memory B cells than control subjects. GC formation in lymph nodes was also impaired in IL-12Rβ1-deficient subjects. Consistently, the avidity of tetanus toxoid-specific serum antibodies was substantially lower in these subjects than in age-matched controls. Tfh cells in tonsils from control individuals displayed the active form of signal transducer and activator of transcription 4 (STAT4), demonstrating that IL-12 is also acting on Tfh cells in GCs. Thus, our study shows that the IL-12-STAT4 axis is associated with the development and the functions of Tfh cells in vivo in humans.
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA. nathalis@baylorhealth.edu
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schmitt
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.forename: Laure
authors.initials: L
authors.lastname: Bourdery
authors.forename: Salah Eddine
authors.initials: SE
authors.lastname: Bentebibel
authors.forename: Stephanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.forename: Fran
authors.initials: F
authors.lastname: Hamlin
authors.forename: Mau V
authors.initials: MV
authors.lastname: Tran
authors.forename: Derek
authors.initials: D
authors.lastname: Blankenship
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Savino
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007156:Immunologic Memory / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D014066:Palatine Tonsil / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D053707:Receptors, Interleukin-12 / Q000172:deficiency* / Q000502:physiology*; D050797:STAT4 Transcription Factor / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D053759:Interleukin-23; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D018664:Interleukin-12