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ResearchIn-Press PreviewImmunologyTransplantation Free access | 10.1172/jci.insight.121782

CCR4 expression on host T cells is a driver for alloreactive responses and lung rejection

Vyacheslav Palchevskiy, Ying Ying Xue, Rita Kern, Stephen S. Weigt, Aric L. Gregson, Sophie X. Song, Michael C. Fishbein, Cory M. Hogaboam, David M. Sayah, Joseph P. Lynch, III, Michael P. Keane, David G. Brooks, and John A. Belperio

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Published May 14, 2019 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.121782.
Copyright © 2019, American Society for Clinical Investigation
Published May 14, 2019 - Version history
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Abstract

Despite current immunosuppressive strategies, long-term lung transplant outcomes remain poor due to rapid allogenic responses. Using a stringent mouse model of allo-airway transplantation, we identify the CCR4-ligand axis as a central node driving secondary lymphoid tissue homing and activation of the allogeneic T cells that prevent long-term allograft survival. CCR4 deficiency on transplant recipient T cells diminishes allograft injury and when combined with CTLA4-Ig leads to an unprecedented long-term lung allograft accommodation. Thus, we identify CCR4-ligand interactions as a central mechanism driving allogeneic transplant rejection and suggest it as a potential target to enhance long-term lung transplant survival.

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  • Version 2 (June 20, 2019): Electronic publication

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