A phenotypically and functionally distinct human T H 2 cell subpopulation is associated with allergic disorders.

Allergen-specific type 2 helper T (T _H 2) cells play a central role in initiating and orchestrating the allergic and asthmatic inflammatory response pathways. One major factor limiting the use of such atopic disease-causing T cells as both therapeutic targets and clinically useful biomarkers is the lack of an accepted methodology to identify and differentiate these cells from overall nonpathogenic T _H 2 cell types. We have described a subset of human memory T _H 2 cells confined to atopic individuals that includes all allergen-specific T _H 2 cells. These cells are terminally differentiated CD4 ⁺ T cells (CD27 ^- and CD45RB ^- ) characterized by coexpression of CRT _H 2, CD49d, and CD161 and exhibit numerous functional attributes distinct from conventional T _H 2 cells. Hence, we have denoted these cells with this stable allergic disease-related phenotype as the T _H 2A cell subset. Transcriptome analysis further revealed a distinct pathway in the initiation of pathogenic responses to allergen, and elimination of these cells is indicative of clinical responses induced by immunotherapy. Together, these findings identify a human T _H 2 cell signature in allergic diseases that could be used for response-monitoring and designing appropriate immunomodulatory strategies.
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