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T-cell trafficking plays an essential role in tumor immunity

Abstract

Distinct populations of effector memory T cells use different homing receptors to traffic to the skin and gut. Whether tissue-selective T cells are needed for early rejection of a neoplasm growing in these tissues remains an open question. We chose to study an allogeneic tumor model because growth of such a fully mismatched tumor would signify a profound immune deficit. We implanted allogeneic tumor cells in the skin or gut of mice deficient in either α(1,3) fucosyltransferases IV and VII, enzymes critical for generating E-selectin ligands on skin-homing T cells, or β7 integrin, a component of the α4β7 integrin ligand for the mucosal adressin MAdCAM. During the first 9 days after tumor implantation, FucTVII−/− mice showed a profoundly impaired capacity to reject tumors growing in the skin, but readily rejected tumors implanted in the gut. Rejection of tumors in the skin was even more impaired in mice deficient in both FucTIV and FucTVII. This impairment was corrected by infusion of T cells from normal mice. By contrast, β7 integrin−/− mice showed profoundly impaired rejection of tumors in the gut, but no defect in the skin tumor rejection. These differences were unrelated to antigen recognition or effector function of T cells, since all strains of mice were capable of generating tumor-specific CTLs in vitro against the tumor cell line used in vivo. These results demonstrate that T-cell homing defects in vivo impair immune surveillance of peripheral epithelial tissues in a specific and selective fashion.

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Acknowledgements

We are grateful to Carol Botteron for comments, and John D Omobono and Christina Stephenson for help with preparation of the figures.

Funding

This work was supported by the NIH grants T32 AR07098, R01 AI040124, R01 AR065807, and R37 AI25082 (all to TSK), and was also supported in part by Frontiers: The Heartland Institute for Clinical and Translational Research CTSA KL2RR033177 (awarded to the University of Kansas Medical Center, to JAW). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

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Conflict of interest

The authors declare that they have no conflict of interest.

Correspondence to Thomas S. Kupper.

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cytotoxicity - supplemental data

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