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

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...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2012-01, Vol.36 (1), p.132-141
Main Authors: Markiewicz, Mary A., Wise, Erica L., Buchwald, Zachary S., Pinto, Amelia K., Zafirova, Biljana, Polic, Bojan, Shaw, Andrey S.
Format: Article
Language:English
Subjects:
Animals
Cell Movement - immunology
Cytotoxicity
Diabetes mellitus
Flow Cytometry
Infection
Inflammation
Insulitis
Islets of Langerhans
Islets of Langerhans - metabolism
Ligands
Lymphocytes T
Mice
Mice, Transgenic
NK Cell Lectin-Like Receptor Subfamily K - genetics
NK Cell Lectin-Like Receptor Subfamily K - metabolism
Pancreas
Receptors, Antigen, T-Cell - metabolism
Retinoic acid
T-cell receptor
T-Lymphocytes, Cytotoxic - immunology
Transcription
Transgenic mice
Tretinoin - metabolism
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Summary: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. ► RAE1ε expression in pancreatic islets leads to the recruitment of CTLs via NKG2D ► Recruitment of CTLs to islets induces chemokine expression in islets ► RAE1ε expression in pancreatic islets induces a mild insulitis in older mice ► Inflammation and viral infection enhances insulitis development
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2011.11.014