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. 2013 Aug 2;4:208. doi: 10.3389/fimmu.2013.00208

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Copyright © 2013 Hall, Tran, Verma, Plain, Robinson, Nomura and Hodgkinson.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Shows how IL-4 without TCR engagement with specific Ag induces polyclonal expansion of nT_reg. If antigen is present a minority population of nT_reg that have TCR specific for antigen are activated to Ts2 by IL-4. Ts2 cells express IL-5Rα, IFN-γ, and FoxP3 but not IL-5, IFNGR, IL-12Rβ2, GATA3, T-bet, or IL-2. Ts2 cells have increased potency over nT_reg of at least 10-fold that is antigen specific. The second step of activation of nT_reg converts antigen specific Ts2 to Th2-like T_reg and requires specific antigen and Th2 cytokines, probably IL-5. Th2-like T_reg express IRF4 with FoxP3 and Th2 cytokines IL-4 and IL-5.