title: Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets.
abstract: Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional "roadmap" of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an "anergic" Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls. These findings show that sustained success, even after immunotherapy is withdrawn, is associated with the induction, expansion, and maintenance of immunotherapy-specific memory and naive T-cell phenotypes as early as 3 mo into immunotherapy. These results suggest an approach for immune monitoring participants undergoing immunotherapy to predict the success of future treatment and could have implications for immunotherapy targets in other diseases like cancer, autoimmune disease, and transplantation.
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305;
authors.forename: John F
authors.initials: JF
authors.lastname: Ryan
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305;
authors.forename: Rachel
authors.initials: R
authors.lastname: Hovde
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305;
authors.forename: Jacob
authors.initials: J
authors.lastname: Glanville
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305;
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Lyu
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305;
authors.forename: Xuhuai
authors.initials: X
authors.lastname: Ji
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305;
authors.forename: Sheena
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Health Research and Policy, Stanford University, Stanford, CA 94305; Department of Statistics, Stanford University, Stanford, CA 94305;
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tibshirani
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305;
authors.forename: David C
authors.initials: DC
authors.lastname: Jay
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305;
authors.forename: Scott D
authors.initials: SD
authors.lastname: Boyd
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305;
authors.forename: R Sharon
authors.initials: RS
authors.lastname: Chinthrajah
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5428; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford University, Stanford, CA 94305 mmdavis@stanford.edu knadeau@stanford.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5428;
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5428;
authors.forename: Holden T
authors.initials: HT
authors.lastname: Maecker
authors.affiliation: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Pulmonary and Critical Care Medicine, Institute of Immunity, Transplantation, and Infectious Diseases, Stanford University, Stanford, CA 94305; mmdavis@stanford.edu knadeau@stanford.edu.
authors.forename: Kari C
authors.initials: KC
authors.lastname: Nadeau
mesh_terms: D000485:Allergens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D016176:T-Lymphocyte Subsets
chemical_list: D000485:Allergens
keywords: T cells; anergy; gene expression; immunotherapy; tolerance
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