A phenotypically and functionally distinct human T_H2 cell subpopulation is associated with allergic disorders

Allergen-specific type 2 helper T (T_H2) 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_H2 cell types. We have described a subset of human memory T_H2 cells confined to atopic individuals that includes all allergen-specific T_H2 cells. These cells are terminally differentiated CD4⁺ T cells (CD27^- and CD45RB^-) characterized by coexpression of CRT_H2, CD49d, and CD161 and exhibit numerous functional attributes distinct from conventional T_H2 cells. Hence, we have denoted these cells with this stable allergic disease-related phenotype as the T_H2A 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_H2 cell signature in allergic diseases that could be used for response-monitoring and designing appropriate immunomodulatory strategies.