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In this study, the Ts6 and Ts15 toxins isolated from <jats:italic>Tityus serrulatus<\/jats:italic> (Ts) were investigated for their immunosuppressant roles on <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> cell subsets: naive, effector (<jats:styled-content style=\"fixed-case\">T<jats:sub>EF<\/jats:sub><\/jats:styled-content>), central memory (<jats:styled-content style=\"fixed-case\">T<jats:sub>CM<\/jats:sub><\/jats:styled-content>) and effector memory (<jats:styled-content style=\"fixed-case\">T<jats:sub>EM<\/jats:sub><\/jats:styled-content>). The electrophysiological assays confirmed that both toxins were able to block Kv1.3 channels. Interestingly, an extended Kv channel screening shows that Ts15 blocks Kv2.1 channels. Ts6 and Ts15 significantly inhibit the proliferation of <jats:styled-content style=\"fixed-case\">T<jats:sub>EM<\/jats:sub><\/jats:styled-content> cells and interferon\u2010<jats:italic>\u03b3<\/jats:italic> production; however, Ts15 also inhibits other <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> cell subsets (naive, <jats:styled-content style=\"fixed-case\">T<jats:sub>EF<\/jats:sub><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">T<jats:sub>CM<\/jats:sub><\/jats:styled-content>). Based on the Ts15 inhibitory effect of proliferation of all <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> cell subsets, and based on its blocking effect on Kv2.1, we investigated the Kv2.1 expression in T cells. The assays showed that <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> cells express the Kv2.1 channels mainly extracellularly with <jats:styled-content style=\"fixed-case\">T<jats:sub>CM<\/jats:sub><\/jats:styled-content> cells expressing the highest number of Kv2.1 channels. We also provide <jats:italic>in vivo<\/jats:italic> experimental evidence to the protective effect of Ts6 and Ts15 on delayed\u2010type hypersensitivity reaction. Altogether, this study presents the immunosuppressive behaviour of Ts6 and Ts15 toxins, indicating that these toxins could be promising candidates for autoimmune disease therapy. Moreover, this is the first report illustrating the involvement of a novel K<jats:sup>+<\/jats:sup> channel subtype, Kv2.1, and its distribution in T\u2010cell subsets.<\/jats:p>","DOI":"10.1111\/imm.12559","type":"journal-article","created":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T15:39:40Z","timestamp":1448293180000},"page":"240-250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Immunosuppressive evidence of <i>Tityus serrulatus<\/i> toxins Ts6 and Ts15: insights of a novel K<sup>+<\/sup> channel pattern in T cells"],"prefix":"10.1111","volume":"147","author":[{"given":"Manuela B.","family":"Pucca","sequence":"first","affiliation":[{"name":"Department of Physics and Chemistry School of Pharmaceutical Sciences of Ribeir\u00e3o Preto University of S\u00e3o Paulo Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tha\u00eds B.","family":"Bertolini","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology School of Medicine of Ribeir\u00e3o Preto University of S\u00e3o Paulo Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe A.","family":"Cerni","sequence":"additional","affiliation":[{"name":"Department of Physics and Chemistry School of Pharmaceutical Sciences of Ribeir\u00e3o Preto University of S\u00e3o Paulo Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karla C. 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