Potential non-T cells source of interleukin-4 in food allergy

Background: Recently, a study from the Consortium of Food Allergy Research (CoFAR) showed that allergen-induced IL-4 expression in CD25⁺ mononuclear cells was increased in allergic patients. However, they did not find the expected increase in GATA-3 expression, suggesting that allergen-induced IL-4 might not be of T-cell origin. We sought to determine whether other cell types were responsible for the increased IL-4 expression in the CD25⁺ cell population. Methods: Comparing six allergic patients and six healthy controls, we analyzed the CD25⁺ isolated population from PBMC for the presence of potential IL-4-expressing non-T cells. We also compared spontaneous expression levels of surface markers (CD203c, CD63, CD25, and HLA-DR) on basophils from whole blood of 42 peanut-allergic patients and from 12 non-atopic controls. Expression of these markers was also evaluated following basophil activation in eight peanut-allergic patients selected from the previous cohort. Results: In addition to CD4⁺ T cells, a substantial proportion of non-T cells were found in the CD25⁺-isolated cell population: basophils, NK, and NK-T cells with a mean percentage ± s.e.m. of 5.24 ± 0.63%, 6.65 ± 1.01%, and 6.01 ± 1.04%, respectively. The majority of these cells exhibited positive intracytoplasmic staining for IL-4. Expression of CD63 and CD25 was significantly higher in allergic patients compared with controls (p < 0.05). Interestingly, we found a significantly higher proportion of activated basophils expressing HLA-DR, compared with non-activated basophils (p < 0.05). Conclusions: Our results support the suggested key role of non-T cells secreting IL-4 in food allergy, particularly basophils, which may also play a central role in antigen presentation.