Identification of T- and B-Cell Subsets That Expand in the Central and Peripheral Lymphoid Organs during the Establishment of Nut Allergy in an Adjuvant-Free Mouse Model

Nut allergies are potentially fatal and rarely outgrown for reasons that are not well understood. Phenotype of T- and B-cell subsets that expand during the early stages of nut allergy is largely unknown. Here we studied this problem using a novel mouse model of nut allergy. Mice were rendered hazelnut allergic by a transdermal sensitization/oral elicitation protocol. Using flow cytometry, the T- and B-cell phenotype in the bone marrow (BM), spleen, and the mesenteric lymph node (MLN) of allergic and control mice was analyzed. Nut allergic mice exhibited an expansion of CD4+ CD62L？ T cells in BM and spleen; a similar trend was noted in the MLN. There was expansion of CD80+ B cells in BM and spleen and MLN and CD62L？ cells in BM and spleen. Interestingly, among CD80+ B cells, significant proportion was CD73？ particularly in the MLN. These data demonstrate that during the early establishment of hazelnut allergy there is (i) expansion of CD4+CD62L？ T-cell subsets in both the BM and the periphery, (ii) expansion of CD80+ and CD62L？ B-cell subsets in BM and the periphery, and (iii) a significant downregulation of CD73 on a subset of B cells in MLN. 1. Introduction Food allergies such as tree nut allergies are potentially fatal group of immune-mediated disorders [1]. Recent studies demonstrate that both the prevalence and severity of food allergies are escalating for reasons that are not well understood at present [1, 2]. Tree nut allergies, along with peanut allergy, are the leading causes of food-induced systemic anaphylaxis in USA and European countries [3]. Furthermore, once individuals are sensitized, there is a very low potential for outgrowing tree nut allergies [4, 5]. Consequently, they are considered not only serious but also persistent health problems for rest of the life of sensitized subjects [4, 5]. The specific identity of T- and B-cell subsets that expand during the early stages of establishment of life-threatening nut allergies is largely unknown at present. Notably, most of the current knowledge about early expansion and establishment of immune memory cells comes from studies of infectious diseases [6–12]. Knowledge about identity of such immune cells is urgently needed for potential therapeutic targeting in nut allergies. We have previously reported an adjuvant-free mouse model of tree nut allergy using hazelnut as a model tree nut [13]. This model employs a protocol combining transdermal sensitization followed by oral allergen challenge to elicit systemic anaphylaxis [13–15]. Furthermore, hazelnut allergy, once established, remains