期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 135, 期 5, 页码 1283-1292出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2014.11.010
关键词
Peanut allergy; oral immunotherapy; sublingual immunotherapy; sustained unresponsiveness; basophil activation; dendritic cells; food allergy
资金
- National Center for Advancing Translational Sciences (NCATS) [UL1TR001079]
- NIH Roadmap for Medical Research
- Research Training in Pediatric Allergy and Immunology [5T32AI007007]
- NIH [K23AI091869, AI079853]
- ARTrust Faculty Development Award
- Johns Hopkins University Clinician Scientist Award
- NIH Asthma and Allergic Diseases Cooperative Research Centers grant [U19AI070345-01]
- Food Allergy Research and Education grant
- Eudowood Foundation
- Winkelstein fellowship
- Division of Intramural Research, NIAID, NIH
- National Center for Research Resources
- National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health [101872]
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 T(H)2 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: OITand 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.
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