Functional Profile of Antigen Specific CD4+ T Cells in the Immune Response to Phospholipase A1 Allergen from Polybia paulista Venom.

Luís Gustavo Romani Fernandes,Amilcar Perez-Riverol,Ricardo De Lima Zollner,Márcia Regina Brochetto-Braga,Murilo Luiz Bazon,Débora Moitinho Abram

doi:10.3390/toxins12060379

Luís Gustavo Romani Fernandes, Amilcar Perez-Riverol + Show 4 more

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https://doi.org/10.3390/toxins12060379

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Abstract

Insect venom can cause systemic allergic reactions, including anaphylaxis. Improvements in diagnosis and venom immunotherapy (VIT) are based on a better understanding of an immunological response triggered by venom allergens. Previously, we demonstrated that the recombinant phospholipase A1 (rPoly p 1) from Polybia paulista wasp venom induces specific IgE and IgG antibodies in sensitized mice, which recognized the native allergen. Here, we addressed the T cell immune response of rPoly p 1-sensitized BALB/c mice. Cultures of splenocytes were stimulated with Polybia paulista venom extract and the proliferation of CD8+ and CD4+ T cells and the frequency of T regulatory cells (Tregs) populations were assessed by flow cytometry. Cytokines were quantified in cell culture supernatants in ELISA assays. The in vitro stimulation of T cells from sensitized mice induces a significant proliferation of CD4+ T cells, but not of CD8+ T cells. The cytokine pattern showed a high concentration of IFN-γ and IL-6, and no significant differences to IL-4, IL-1β and TGF-β1 production. In addition, the rPoly p 1 group showed a pronounced expansion of CD4+CD25+FoxP3+ and CD4+CD25-FoxP3+ Tregs. rPoly p 1 sensitization induces a Th1/Treg profile in CD4+ T cell subset, suggesting its potential use in wasp venom immunotherapy.

Highlights

Insect sting allergy accounts for 14% of severe cases of allergic reactions in Latin America, resulting in considerable morbidity and significant expenses for the treatment of patients [1]
We demonstrated that the expression of Poly p 1 in E. coli resulted in an immunologically active allergen. rPoly p 1 reactivity with sera from P. paulista-allergic patients was compared with P. paulista venom extract and purified native Poly p 1 [12]
CD4+ CD25+ Foxp3+ T regulatory cells (Tregs), which, by the increase in lymph-node-homing receptors such as CD62L, CD11a and CCR7, preferentially migrates to secondary lymphoid organs to suppress T-cell effector responses. This fact could evidence the importance of this Treg population to the efficiency of we observed a significant increase in Foxp3+ Tregs that do not express the CD25 marker in the CD4+ T cell population from rPoly p 1-sensitized mice

Summary

Introduction

Insect sting allergy accounts for 14% of severe cases of allergic reactions in Latin America, resulting in considerable morbidity and significant expenses for the treatment of patients [1]. The most clinically relevant venom allergies involve the Hymenoptera order such as bees (Apoidea), wasps (Vespoidea) and ants (Formicidae) [2]. Toxins 2020, 12, 379 in the southeastern region It presents a highly aggressive behavior and is related to most cases of allergic reactions, including anaphylaxis, involving wasp sting accidents in this region [3]. To other clinically relevant insects, the venom of P. paulista is a complex mix of low molecular weight compounds, linear polycationic peptides and allergens [4]. While small compounds and peptides are involved in toxic and local reactions, venom allergens often cause moderate to severe systemic hypersensitivity reactions, including life-threatening anaphylaxis

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