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Heterogeneity of cockroach allergen-specific T cell responses in allergic sensitized children
  • +23
  • Ricardo da Silva Antunes,
  • Aaron Sutherland,
  • April Frazier,
  • Veronique Schulten,
  • Anna PomĂ©s,
  • Jill Glesner,
  • Agustin Calatroni,
  • Matthew Altman,
  • Robert A. Wood,
  • George O'Connor,
  • Jackie Pongracic,
  • Gurjit Khurana Hershey,
  • Carolyn Kercsmar,
  • Rebecca Gruchalla,
  • Michelle Gill,
  • Andrew Liu,
  • Edward Zoratti,
  • Meyer Kattan,
  • Paula Busse,
  • Leonard Bacharier,
  • Stephen Teach,
  • Lisa Wheatley,
  • Alkis Togias,
  • William Busse,
  • Daniel Jackson,
  • Alessandro Sette
Ricardo da Silva Antunes
La Jolla Institute for Immunology
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Aaron Sutherland
La Jolla Institute for Immunology
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April Frazier
La Jolla Institute for Immunology
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Veronique Schulten
La Jolla Institute for Immunology
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Anna Pomés
Indoor Biotechnologies
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Jill Glesner
Indoor Biotechnologies
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Agustin Calatroni
Rho, Inc.
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Matthew Altman
University of Washington
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Robert A. Wood
Johns Hopkins University School of Medicine
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George O'Connor
Boston University School of Medicine
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Jackie Pongracic
Ann and Robert H Lurie Children's Hospital of Chicago
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Gurjit Khurana Hershey
Cincinnati Children's Hospital Medical Center
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Carolyn Kercsmar
Cincinnati Children's Hospital Medical Center
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Rebecca Gruchalla
The University of Texas Southwestern Medical Center Department of Pediatrics
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Michelle Gill
University of Texas Southwestern Medical Center at Dallas
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Andrew Liu
National Jewish Health
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Edward Zoratti
Henry Ford Health System
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Meyer Kattan
Columbia University College of Physicians and Surgeons
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Paula Busse
Icahn School of Medicine at Mount Sinai
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Leonard Bacharier
Monroe Carell Jr Children’s Hospital at Vanderbilt University Medical Center
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Stephen Teach
Children's National Health System
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Lisa Wheatley
National Institute of Allergy and Infectious Diseases
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Alkis Togias
National institute of Health
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William Busse
University of Wisconsin
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Daniel Jackson
University of Wisconsin Madison
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Alessandro Sette
La Jolla Institute for Immunology

Corresponding Author:[email protected]

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Abstract

BACKGROUND: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. RESULTS: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFN production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. CONCLUSIONS: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.