@article{69bf5d40dc6e4dc8abb3d9713b7fd1d5,
title = "Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease",
abstract = "A major function of NKG2D linking innate and adaptive immunity is to upregulate antigen-specific CTL-mediated cytotoxicity in tissues expressing stress-induced NKG2D ligands, such as MIC, by coactivating TCR signaling. Here, we show that, under conditions of dysregulated IL15 expression in vivo in patients with celiac disease and in vitro in healthy individuals, multiple steps of the NKG2D/DAP10 signaling pathway leading to ERK and JNK activation are coordinately primed to activate direct cytolytic function independent of TCR specificity in effector CD8 T cells. These findings may not only explain previous reports of transformation of CTL into NK-like {"}lymphokine- activated killers{"} (LAK cells) under high doses of IL2 (a substitute for IL15) but may also have significant implications for understanding and treating immunopathological diseases.",
author = "Bertrand Meresse and Zhangguo Chen and Cezary Ciszewski and Maria Tretiakova and Govind Bhagat and Krausz, {Thomas N.} and Raulet, {David H.} and Lanier, {Lewis L.} and Veronika Groh and Thomas Spies and Ebert, {Ellen C.} and Green, {Peter H.} and Bana Jabri",
note = "Funding Information: The authors are grateful to A. Bendelac for discussions and critical reading of the manuscript, Theodore Karrison for help with statistical analysis, John Hart and Terry Li for help in the realization of the immunohistochemistry studies, and Bart Eisfelder, Ryan Duggan, and James Marvin for cell sorting. We thank the University of Chicago DDRC and the University of Chicago and the Columbia Presbyterian Hospital Celiac Disease Centers for their support. This work is supported by a RO1 DK 58727-01A1 grant from NIH. B.M. was supported by a grant of the Fondation pour la recherche medicale (FRM). D.H.R. is supported by NIH grant CA093678. L.L.L. is an American Cancer Society Research Professor and supported by NIH grant CA89294. V.G. and T.S. are supported by R01 A1 30581.",
year = "2004",
month = sep,
doi = "10.1016/j.immuni.2004.06.020",
language = "English",
volume = "21",
pages = "357--366",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "3",
}