title: Abundance and specificity of influenza reactive circulating memory follicular helper and non-follicular helper CD4 T cells in healthy adults.
abstract: CD4 T-cell responses are functionally complex and regulate many aspects of innate and adaptive immunity. Follicular helper (Tfh) cells are CD4 T cells specialized to support B-cell production of isotype-switched, high-affinity antibody. So far, studies of Tfh cells in humans have focused on their differentiation requirements, with little research devoted to their antigen specificity. Here, after separating circulating human memory CD4 T cells based on expression of CXCR5, a signature marker of Tfh, we have quantified and assayed the influenza protein antigen specificity of blood Tfh cells and CD4 T cells lacking this marker. Through the use of peptide pools derived from nucleoprotein (NP) or haemagglutinin (HA) and a panel of human donors, we have discovered that circulating Tfh cells preferentially recognize peptide epitopes from HA while cells lacking CXCR5 are enriched for specificity toward NP. These studies suggest that reactive CD4 T cells specific for distinct viral antigens may have generalized differences in their functional potential due to their previous stimulation history.
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Leddon
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Richards
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Sant
mesh_terms: D053330:4-1BB Ligand / Q000276:immunology; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015704:CD4 Antigens / Q000096:biosynthesis; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D037181:Lectins, C-Type / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008875:Middle Aged; D009698:Nucleoproteins / Q000276:immunology*; D054380:Receptors, CXCR5 / Q000096:biosynthesis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D055815:Young Adult; D000099192:CD69 Antigens
chemical_list: D053330:4-1BB Ligand; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D006389:Hemagglutinins, Viral; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D009698:Nucleoproteins; D054380:Receptors, CXCR5; D000099192:CD69 Antigens; C095085:CXCR5 protein, human; C505974:TNFSF9 protein, human
keywords: B cells; CD4 T cells; influenza virus; vaccines