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

Abstract

Allergen-specific type 2 helper T (TH2) 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 TH2 cell types. We have described a subset of human memory TH2 cells confined to atopic individuals that includes all allergen-specific TH2 cells. These cells are terminally differentiated CD4+ T cells (CD27− and CD45RB−) characterized by coexpression of CRTH2, CD49d, and CD161 and exhibit numerous functional attributes distinct from conventional TH2 cells. Hence, we have denoted these cells with this stable allergic disease–related phenotype as the TH2A 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 TH2 cell signature in allergic diseases that could be used for response-monitoring and designing appropriate immunomodulatory strategies.

PPAR-γ in innate and adaptive lung immunity

“…Furthermore, we could show the relevance of these findings also for humans, because PPAR‐γ was found to be highly expressed in human memory CRTh2 + Th2 cells . These results were corroborated by recent evidence that identified PPAR‐γ as well as CRTh2, IL‐5, and IL‐9 to be highly expressed in a subset of memory Th2 cells are only present in allergic individuals . The importance of this discovery was further highlighted by evidence that this highly pathogenic Th2 subset is potentially one of the main factors driving steroid‐resistant asthma, a key health problem associated with the treatment of this disease .…”

Dissecting human ILC heterogeneity: more than just three subsets

“…CD161 is expressed by all ILCs, with the exception of some NK and ILC3 cells . Interestingly, differentiated Th1, Th2 and Th17 CD4 + T cells also express CD161 . On T cells, CD161 can act as costimulatory or co‐inhibitory receptors .…”

Recent developments and highlights in food allergy

“…This subset produces a very stable secretion pattern with significantly more IL‐5 and IL‐9 production and a higher percentage of type 2 cytokine double‐, triple‐, or quadruple‐positive cells compared to Th2 cells. Th2a also show a higher mRNA expression of IL‐25, IL‐33 and TSLP receptors …”