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Science 334 (6060): 1293-1297

Copyright © 2011 by the American Association for the Advancement of Science

The Intraepithelial T Cell Response to NKG2D-Ligands Links Lymphoid Stress Surveillance to Atopy

Jessica Strid,1,2 Olga Sobolev,1,2 Biljana Zafirova,3 Bojan Polic,3 Adrian Hayday1,2,*

Abstract: Epithelial cells respond to physicochemical damage with up-regulation of major histocompatibility complex–like ligands that can activate the cytolytic potential of neighboring intraepithelial T cells by binding the activating receptor, NKG2D. The systemic implications of this lymphoid stress-surveillance response, however, are unknown. We found that antigens encountered at the same time as cutaneous epithelial stress induced strong primary and secondary systemic, T helper 2 (TH2)–associated atopic responses in mice. These responses required NKG2D-dependent communication between dysregulated epithelial cells and tissue-associated lymphoid cells. These data are germane to uncertainty over the afferent induction of TH2 responses and provide a molecular framework for considering atopy as an important component of the response to tissue damage and carcinogenesis.

1 London Research Institute, Cancer Research UK, London WC2A 3LY, UK.
2 Peter Gorer Department of Immunobiology, King’s College School of Medicine at Guy’s Hospital, London SE1 9RT, UK.
3 Department of Histology and Embryology, University of Rijeka School of Medicine, Brace Branchetta 20, HR-51000 Rijeka, Croatia.

* To whom correspondence should be addressed. E-mail: adrian.hayday{at}

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