title: Transcriptional profile of tuberculosis antigen-specific T cells reveals novel multifunctional features.
abstract: In latent tuberculosis infection (LTBI) spread of the bacteria is contained by a persistent immune response, which includes CD4(+) T cells as important contributors. In this study we show that TB-specific CD4(+) T cells have a characteristic chemokine expression signature (CCR6(+)CXCR3(+)CCR4(-)), and that the overall number of these cells is significantly increased in LTBI donors compared with healthy subjects. We have comprehensively characterized the transcriptional signature of CCR6(+)CXCR3(+)CCR4(-) cells and found significant differences to conventional Th1, Th17, and Th2 cells, but no major changes between healthy and LTBI donors. CCR6(+)CXCR3(+)CCR4(-) cells display lineage-specific signatures of both Th1 and Th17 cells, but also have a unique gene expression program, including genes associated with susceptibility to TB, enhanced T cell activation, enhanced cell survival, and induction of a cytotoxic program akin to CTL cells. Overall, the gene expression signature of CCR6(+)CXCR3(+)CCR4(-) cells reveals characteristics important for controlling latent TB infections.
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and.
authors.forename: Cecilia Lindestam
authors.initials: CL
authors.lastname: Arlehamn
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and.
authors.forename: Gregory
authors.initials: G
authors.lastname: Seumois
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and.
authors.forename: Anna
authors.initials: A
authors.lastname: Gerasimova
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and.
authors.forename: Charlie
authors.initials: C
authors.lastname: Huang
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yue
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and Clinical and Experimental Sciences, Southampton National Institute for Health Research Respiratory Biomedical Research Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, United Kingdom.
authors.forename: Pandurangan
authors.initials: P
authors.lastname: Vijayanand
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and bpeters@liai.org.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
mesh_terms: D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D055985:Latent Tuberculosis / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D054398:Receptors, CCR4 / Q000096:biosynthesis*; D054399:Receptors, CCR6 / Q000096:biosynthesis*; D054367:Receptors, CXCR3 / Q000096:biosynthesis*; D017423:Sequence Analysis, RNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: C515354:CCR4 protein, human; C106311:CCR6 protein, human; C515187:CXCR3 protein, human; D018984:Epitopes, T-Lymphocyte; D054398:Receptors, CCR4; D054399:Receptors, CCR6; D054367:Receptors, CXCR3
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