Suppression of the immunologic response to peanut during immunotherapy is often transient

J Allergy Clin Immunol. 2015 May;135(5):1283-92. doi: 10.1016/j.jaci.2014.11.010. Epub 2014 Dec 24.


Background: Studies suggest that oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for food allergy hold promise; however, the immunologic mechanisms underlying these therapies are not well understood.

Objective: We sought to generate insights into the mechanisms and duration of suppression of immune responses to peanut during immunotherapy.

Methods: Blood was obtained from subjects at baseline and at multiple time points during a placebo-controlled trial of peanut OIT and SLIT. Immunologic outcomes included measurement of spontaneous and stimulated basophil activity by using automated fluorometry (histamine) and flow cytometry (activation markers and IL-4), measurement of allergen-induced cytokine expression in dendritic cell (DC)-T-cell cocultures by using multiplexing technology, and measurement of MHC II and costimulatory molecule expression on DCs by using flow cytometry.

Results: Spontaneous and allergen-induced basophil reactivity (histamine release, CD63 expression, and IL-4 production) were suppressed during dose escalation and after 6 months of maintenance dosing. Peanut- and dust mite-induced expression of TH2 cytokines was reduced in DC-T-cell cocultures during immunotherapy. This was associated with decreased levels of CD40, HLA-DR, and CD86 expression on DCs and increased expression of CD80. These effects were most striking in myeloid DC-T-cell cocultures from subjects receiving OIT. Many markers of immunologic suppression reversed after withdrawal from immunotherapy and in some cases during ongoing maintenance therapy.

Conclusion: OIT and SLIT for peanut allergy induce rapid suppression of basophil effector functions, DC activation, and TH2 cytokine responses during the initial phases of immunotherapy in an antigen-nonspecific manner. Although there was some interindividual variation, in many patients suppression appeared to be temporary.

Keywords: Peanut allergy; basophil activation; dendritic cells; food allergy; oral immunotherapy; sublingual immunotherapy; sustained unresponsiveness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Administration, Sublingual
  • Allergens / administration & dosage
  • Allergens / immunology
  • Arachis / adverse effects
  • Basophils / immunology
  • Basophils / metabolism
  • Biomarkers
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Desensitization, Immunologic*
  • Gene Expression
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology
  • Humans
  • Interleukin-4 / metabolism
  • Peanut Hypersensitivity / genetics
  • Peanut Hypersensitivity / immunology*
  • Peanut Hypersensitivity / therapy*
  • Pilot Projects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tetraspanin 30 / metabolism
  • Treatment Outcome


  • Allergens
  • Biomarkers
  • Cytokines
  • HLA-DR Antigens
  • Tetraspanin 30
  • Interleukin-4