A phenotypically and functionally distinct human TH2 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.