title: T cell immunity. Functional heterogeneity of human memory CD4⁺ T cell clones primed by pathogens or vaccines.
abstract: Distinct types of CD4(+) T cells protect the host against different classes of pathogens. However, it is unclear whether a given pathogen induces a single type of polarized T cell. By combining antigenic stimulation and T cell receptor deep sequencing, we found that human pathogen- and vaccine-specific T helper 1 (T(H)1), T(H)2, and T(H)17 memory cells have different frequencies but comparable diversity and comprise not only clones polarized toward a single fate, but also clones whose progeny have acquired multiple fates. Single naïve T cells primed by a pathogen in vitro could also give rise to multiple fates. Our results unravel an unexpected degree of interclonal and intraclonal functional heterogeneity of the human T cell response and suggest that polarized responses result from preferential expansion rather than priming.
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland. Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
authors.forename: Simone
authors.initials: S
authors.lastname: Becattini
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Latorre
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Mele
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Foglierini
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland.
authors.forename: Corinne
authors.initials: C
authors.lastname: De Gregorio
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland.
authors.forename: Antonino
authors.initials: A
authors.lastname: Cassotta
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland.
authors.forename: Blanca
authors.initials: B
authors.lastname: Fernandez
authors.affiliation: Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Kelderman
authors.affiliation: Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Ton N
authors.initials: TN
authors.lastname: Schumacher
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland.
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland. Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland. federica.sallusto@irb.usi.ch.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D014612:Vaccines