Regulatory T cells induce activation rather than suppression of human basophils

Basophils are a rare granulocyte population that has been associated with allergic and inflammatory responses. It is essential to understand the regulatory mechanisms by which basophils are kept in check, considering the impact of dysregulated basophil function on immune responses under different pathological conditions. Among immunoregulatory cells, CD4⁺CD25⁺FoxP3⁺ regulatory T cells (T_regs) are the key players that maintain immune tolerance. The mechanisms by which T_regs regulate and suppress diverse immune cell subsets have been studied extensively, but the impact of T_regs on basophil functions is not well understood. We report that human basophils are refractory to T_reg-mediated suppression and found that T_regs stimulate resting basophils to induce the expression of activation markers including CD69, CD203c, and CD13 and the release of basophil cytokines including IL-13, IL-8, and IL-4. Mechanistically, T_regs could induce human basophil activation via IL-3 and STAT5 activation, whereas cellular contact was dispensable. Inhibition of either IL-3-IL-3 receptor interactions or STAT5 phosphorylation abrogated T_reg-mediated activation of basophils. These results provide evidence of direct positive effects that human T_regs have on basophil activation and reveal a previously unrecognized feature of this cell subset well known for immunosuppressive functions.