A phenotypically and functionally distinct human T2 cell subpopulation is associated with allergic disorders.

Allergen-specific type 2 helper T (T2) 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 T2 cell types. We have described a subset of human memory T2 cells confined to atopic individuals that includes all allergen-specific T2 cells. These cells are terminally differentiated CD4 T cells (CD27 and CD45RB) characterized by coexpression of CRT2, CD49d, and CD161 and exhibit numerous functional attributes distinct from conventional T2 cells. Hence, we have denoted these cells with this stable allergic disease-related phenotype as the T2A 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 T2 cell signature in allergic diseases that could be used for response-monitoring and designing appropriate immunomodulatory strategies.