Regulatory T cells induce activation rather than suppression of human basophils

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Science Immunology  25 May 2018:
Vol. 3, Issue 23, eaan0829
DOI: 10.1126/sciimmunol.aan0829

Unexpected basophil activation

Basophils are granulocytes that exist at a relatively rare frequency in the blood but are critical mediators of allergic and inflammatory responses. Regulatory T cells (Tregs) are known to suppress the functions of different immune cells, and Sharma et al. now examine how Tregs regulate basophil functions. Unexpectedly, they observed that resting human basophils are activated and not suppressed in the presence of Tregs. These activated basophils express activation markers (CD69, CD203c, and CD13) and release IL-4, IL-8, and IL-13. Treg-induced activation of basophils involves IL-3 and STAT5 but was not contact-dependent. These results now describe an activating effect mediated by Tregs and provide insight into how basophils are regulated.


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 (Tregs) are the key players that maintain immune tolerance. The mechanisms by which Tregs regulate and suppress diverse immune cell subsets have been studied extensively, but the impact of Tregs on basophil functions is not well understood. We report that human basophils are refractory to Treg-mediated suppression and found that Tregs 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, Tregs 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 Treg-mediated activation of basophils. These results provide evidence of direct positive effects that human Tregs have on basophil activation and reveal a previously unrecognized feature of this cell subset well known for immunosuppressive functions.

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