title: Spaceflight impairs antigen-specific tolerance induction in vivo and increases inflammatory cytokines.
abstract: The health risks of a dysregulated immune response during spaceflight are important to understand as plans emerge for humans to embark on long-term space travel to Mars. In this first-of-its-kind study, we used adoptive transfer of T-cell receptor transgenic OT-II CD4 T cells to track an in vivo antigen-specific immune response that was induced during the course of spaceflight. Experimental mice destined for spaceflight and mice that remained on the ground received transferred OT-II cells and cognate peptide stimulation with ovalbumin (OVA) 323-339 plus the inflammatory adjuvant, monophosphoryl lipid A. Control mice in both flight and ground cohorts received monophosphoryl lipid A alone without additional OVA stimulation. Numbers of OT-II cells in flight mice treated with OVA were significantly increased by 2-fold compared with ground mice treated with OVA, suggesting that tolerance induction was impaired by spaceflight. Production of proinflammatory cytokines were significantly increased in flight compared with ground mice, including a 5-fold increase in IFN-γ and a 10-fold increase in IL-17. This study is the first to show that immune tolerance may be impaired in spaceflight, leading to excessive inflammatory responses.
authors.affiliation: *Department of Surgery and Department of Medicine, University of California, San Franscisco, San Francisco, California, USA; and Northern California Institute for Research and Education, San Francisco, California, USA tammy.chang@ucsf.edu.
authors.forename: Tammy T
authors.initials: TT
authors.lastname: Chang
authors.affiliation: *Department of Surgery and Department of Medicine, University of California, San Franscisco, San Francisco, California, USA; and Northern California Institute for Research and Education, San Francisco, California, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Spurlock
authors.affiliation: *Department of Surgery and Department of Medicine, University of California, San Franscisco, San Francisco, California, USA; and Northern California Institute for Research and Education, San Francisco, California, USA.
authors.forename: Tara Lynne T
authors.initials: TL
authors.lastname: Candelario
authors.affiliation: *Department of Surgery and Department of Medicine, University of California, San Franscisco, San Francisco, California, USA; and Northern California Institute for Research and Education, San Francisco, California, USA.
authors.forename: S Marlene
authors.initials: SM
authors.lastname: Grenon
authors.affiliation: *Department of Surgery and Department of Medicine, University of California, San Franscisco, San Francisco, California, USA; and Northern California Institute for Research and Education, San Francisco, California, USA.
authors.forename: Millie
authors.initials: M
authors.lastname: Hughes-Fulford
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008050:Lipid A / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013026:Space Flight; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D008050:Lipid A; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D010047:Ovalbumin; C048436:monophosphoryl lipid A
keywords: T-cell memory; T-cell tolerance; inflammation; microgravity; transgenic model