title: Lack of allergy to timothy grass pollen is not a passive phenomenon but associated with the allergen-specific modulation of immune reactivity.
abstract: Timothy grass (TG) pollen is a common seasonal airborne allergen associated with symptoms ranging from mild rhinitis to severe asthma.
  
  
  
  The aim of this study was to characterize changes in TG-specific T cell responses as a function of seasonality.
  
  
  
  Peripheral blood mononuclear cells (PBMCs) obtained from allergic individuals and non-allergic controls, either during the pollen season or out of season, were stimulated with either TG extract or a pool of previously identified immunodominant antigenic regions.
  
  
  
  PBMCs from allergic subjects exhibit higher IL-5 and IL-10 responses in season than when collected out of season. In the case of non-allergic subjects, as expected we observed lower IL-5 responses and robust production of IFN-γ compared to allergic individuals. Strikingly, non-allergic donors exhibited an opposing pattern, with decreased immune reactivity in season. The broad down-regulation in non-allergic donors indicates that healthy individuals are not oblivious to allergen exposure, but rather react with an active modulation of responses following the antigenic stimulus provided during the pollen season. Transcriptomic analysis of allergen-specific T cells defined genes modulated in concomitance with the allergen exposure and inhibition of responses in non-allergic donors.
  
  
  
  Magnitude and functionality of T helper cell responses differ substantially in season vs. out of season in allergic and non-allergic subjects. The results indicate the specific and opposing modulation of immune responses following the antigenic stimulation during the pollen season. This seasonal modulation reflects the enactment of specific molecular programmes associated with health and allergic disease.
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hinz
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Seumois
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Gholami
authors.affiliation: Bioinformatics Core Facility, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Greenbaum
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lane
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: White
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Broide
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Schulten
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sidney
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Bakhru
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Oseroff
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Wambre
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: James
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Kwok
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Peters
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Vijayanand
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sette
mesh_terms: D000485:Allergens / Q000276:immunology*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D056747:Immunomodulation; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D010641:Phenotype; D031784:Phleum / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012621:Seasons; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome
chemical_list: D000485:Allergens; D016207:Cytokines; D006680:HLA Antigens; D012333:RNA, Messenger
keywords: T cell response; non-allergic; seasonality; timothy grass