Human subjects without peanut allergy demonstrate T cell–dependent, T H2-biased, peanut-specific cytokine and chemokine responses independent of T H1 expression

Abstract

Peanut allergy is a major cause of anaphylaxis. Regulation of immune responses to peanut allergen, particularly why sensitization does not usually progress to allergic reactions, is not well investigated. Most studies focus exclusively on serologic responses and individuals with peanut allergy. We sought to determine the existence, prevalence, and nature of peanut-specific, T cell-dependent cytokine and chemokine responses of adults who eat peanut without having symptoms. We developed systems to examine specific immunity in peanut-tolerant individuals who had (1) negative histories and negative peanut skin test responses, (2) negative histories and positive peanut skin test responses, and (3) clinically apparent peanut allergy. After primary culture of PBMCs restimulated with whole peanut extract, we quantified responses characteristic of TH1 (IFN-gamma and CXCL10) and TH2-like immunity (IL-5, IL-13, CCL17, and CCL22) using ultrasensitive ELISAs. Antigen-presenting cell costimulatory requirements (CD4, HLA-DR, CD80/86, and cytotoxic T lymphocyte-associated antigen 4 [CTLA4] Ig) were determined. T cell-dependent, peanut-specific IL-5, IL-13, and CCL22 were common in peanut-tolerant individuals, regardless of whether they had positive or negative skin test responses. These were blocked by anti-CD4 and were dependent on CD28/CD86 costimulation. None of the 70 individuals studied had demonstrable IFN-gamma or CXCL10 responses to peanut. All demonstrated TH1 and TH2 responses to the ubiquitous recall antigen streptokinase. Qualitatively similar and quantitatively increasing peanut-specific TH2 responses in the consistent absence of putatively protective TH1 immunity were found in both peanut-tolerant individuals and those with peanut allergy. The continuum of responses between individuals with negative and individuals with positive skin test results, rather than TH1 versus TH2 bias, might be important in peanut allergy.