RAE1ε Ligand Expressed on Pancreatic Islets Recruits NKG2D Receptor-Expressing Cytotoxic T Cells Independent of T Cell Receptor Recognition

Mary A. Markiewicz, Erica L. Wise, Zachary S. Buchwald, Amelia K. Pinto, Biljana Zafirova, Bojan Polic, Andrey S. Shaw

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The mechanisms by which cytotoxic T lymphocytes (CTLs) enter and are retained in nonlymphoid tissue are not well characterized. With a transgenic mouse expressing the NKG2D ligand retinoic acid early transcript 1ε (RAE1ε) in β-islet cells of the pancreas, we found that RAE1 expression was sufficient to induce the recruitment of adoptively transferred CTLs to islets. This was dependent on NKG2D expression by the CTLs and independent of antigen recognition. Surprisingly, the recruitment of CTLs resulted in the subsequent recruitment of a large number of endogenous lymphocytes. Whereas transgenic mice did not develop diabetes, RAE1 expression was sufficient to induce insulitis in older, unmanipulated transgenic mice that was enhanced by viral infection and pancreatic inflammation. These results demonstrate that the expression of an NKG2D ligand in islets is sufficient to recruit CTLs regardless of their antigen specificity and to induce insulitis.

Original languageEnglish
Pages (from-to)132-141
Number of pages10
JournalImmunity
Volume36
Issue number1
DOIs
StatePublished - Jan 27 2012

Bibliographical note

Funding Information:
This work was supported by grants from the NIH (Diabetes Research and Training Center P60 DK020579 to M.A.M. and R37 AI057966 to A.S.S.), the HHMI (A.S.S.), and Croatian Ministry of Science, Education and Sports Grant 062-0621261-1271 (B.P.). We thank X. Wang and Y. Huang (Washington University School of Medicine) for their help with performing the BioPlex assays, H. Virgin and D. Kreamalmeyer (Washington University School of Medicine) for mice, and B. Calderon and E. Unanue (Washington University School of Medicine) for helpful advice and discussion.

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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