{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:07:46Z","timestamp":1787836066446,"version":"build-2784847793"},"reference-count":0,"publisher":"Esmon Publicidad, SA","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Investig Allergol Clin Immunol"],"published-print":{"date-parts":[[2022,12,16]]},"abstract":"<jats:p>Background: Although exposure to stings has been identified as the leading risk factor for anaphylaxis due to Hymenoptera venom allergy, professional beekeepers receive hundreds of stings yearly without developing systemic reactions. Objective: This study aims to analyze the mechanisms underlying bee venom tolerance in beekeepers. Methods: A cross-sectional study was conducted. Participants were recruited and classified into 3 groups: allergic patients (APs), who experienced systemic reactions after bee stings, with a positive intradermal test and specific IgE (sIgE) to Apis mellifera venom (AmV); tolerant beekeepers (TBKs), who received \u226550 stings\/year; and healthy nonexposed controls (HCs). We measured serum levels of sIgE and specific IgG4 (sIgG4) to AmV, rApi m 1, rApi m 2, rApi m 3, Api m 4, rApi m 5, and rApi m10, as well as AmV-induced basophil degranulation, percentage of T-cell subsets, regulatory T cells (Treg), and IL-10 production. Results: Compared with TBKs, APs had high levels of sIgE to AmV and all its allergic components (P&lt;.001), together with a high basophil activation rate (P&lt;.001). Conversely, compared with APs, TBKs had higher levels of sIgG4 (P&lt;.001) and IL-10 (P&lt;.0001), as well as an enhanced CTLA-4+ Treg population (P=.001), expanded Helios\u2013 Treg (P&lt;.003), and reduced type 1 helper T cells (TH1) (P=.008), TH2 (P=.004), and TH17 (P=.007) subsets. Conclusions: The profile of TBKs, which was strongly marked by Treg activity, differed from that of TBKs. This natural tolerance would be led by the expansion of inducible Helios\u2013 Treg cells at the peripheral level. The Helios\u2013 Treg population could be a novel candidate biomarker for monitoring tolerance.<\/jats:p>","DOI":"10.18176\/jiaci.0722","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T17:29:20Z","timestamp":1625074160000},"page":"451-459","source":"Crossref","is-referenced-by-count":4,"title":["Helios-Negative Regulatory T Cells as a Key Factor of Immune Tolerance in Nonallergic Beekeepers"],"prefix":"10.18176","volume":"32","author":[{"given":"B","family":"Ruiz-Leon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Navas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Espinazo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Guler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Alonso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Jurado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Moreno-Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7491","container-title":["Journal of Investigational Allergology and Clinical Immunology"],"original-title":["English"],"deposited":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T10:04:10Z","timestamp":1671185050000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jiaci.org\/summary\/vol32-issue6-num2600"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,16]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12,16]]}},"URL":"https:\/\/doi.org\/10.18176\/jiaci.0722","relation":{},"ISSN":["1018-9068"],"issn-type":[{"value":"1018-9068","type":"print"}],"subject":[],"published":{"date-parts":[[2022,12,16]]}}}