title: Obesity impairs γδ T cell homeostasis and antiviral function in humans.
abstract: Obese patients are susceptible to increased morbidity and mortality associated with infectious diseases such as influenza A virus. γδ T cells and memory αβ T cells play key roles in reducing viral load by rapidly producing IFN-γ and lysing infected cells. In this article we analyze the impact of obesity on T lymphocyte antiviral immunity. Obese donors exhibit a reduction in γδ T cells in the peripheral blood. The severity of obesity negatively correlates with the number of γδ T cells. The remaining γδ T cells have a skewed maturation similar to that observed in aged populations. This skewed γδ T cell population exhibits a blunted antiviral IFN-γ response. Full γδ T cell function can be restored by potent stimulation with 1-Hydroxy-2-methyl-buten-4yl 4-diphosphate (HDMAPP), suggesting that γδ T cells retain the ability to produce IFN-γ. Additionally, γδ T cells from obese donors have reduced levels of IL-2Rα. IL-2 is able to restore γδ T cell antiviral cytokine production, which suggests that γδ T cells lack key T cell specific growth factor signals. These studies make the novel finding that the γδ T cell antiviral immune response to influenza is compromised by obesity. This has important implications for the development of therapeutic strategies to improve vaccination and antiviral responses in obese patients.
authors.affiliation: California State University San Marcos, Department of Biology, 333 South Twin Oaks Drive, San Marcos, CA 92096, United States of America; The Scripps Research Institute, Department of Immunology and Microbial Sciences, 10550 North Torrey Pines Rd, La Jolla, CA 92037, United States of America.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Costanzo
authors.affiliation: The Scripps Research Institute, Department of Immunology and Microbial Sciences, 10550 North Torrey Pines Rd, La Jolla, CA 92037, United States of America.
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Taylor
authors.affiliation: California State University San Marcos, Department of Biology, 333 South Twin Oaks Drive, San Marcos, CA 92096, United States of America.
authors.forename: Shelley
authors.initials: S
authors.lastname: Dutt
authors.affiliation: PHDataGroup 8189 Califa Court, San Diego, CA 92119, United States of America.
authors.forename: Peggy P
authors.initials: PP
authors.lastname: Han
authors.affiliation: Scripps Clinic Research Center, 11025 N. Torrey Pines Rd., La Jolla, CA 92037, United States of America.
authors.forename: Ken
authors.initials: K
authors.lastname: Fujioka
authors.affiliation: California State University San Marcos, Department of Biology, 333 South Twin Oaks Drive, San Marcos, CA 92096, United States of America; The Scripps Research Institute, Department of Immunology and Microbial Sciences, 10550 North Torrey Pines Rd, La Jolla, CA 92037, United States of America.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Jameson
mesh_terms: D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma