APA
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Shapiro, M. R., Yeh, W.-I., Longfield, J. R., Gallagher, J., Infante, C. M., Wellford, S., … Brusko, T. (2020). CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation. Frontiers in Immunology.
Chicago/Turabian
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Shapiro, Melanie R., Wen-I Yeh, Joshua R. Longfield, J. Gallagher, Caridad M. Infante, Sarah Wellford, A. Posgai, et al. “CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation.” Frontiers in Immunology (2020).
MLA
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Shapiro, Melanie R., et al. “CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation.” Frontiers in Immunology, 2020.
BibTeX Click to copy
@article{melanie2020a,
title = {CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation},
year = {2020},
journal = {Frontiers in Immunology},
author = {Shapiro, Melanie R. and Yeh, Wen-I and Longfield, Joshua R. and Gallagher, J. and Infante, Caridad M. and Wellford, Sarah and Posgai, A. and Atkinson, M. and Campbell-Thompson, M. and Lieberman, S. and Serreze, D. and Geurts, A. and Chen, Yi-Guang and Brusko, T.}
}
The costimulatory molecule CD226 is highly expressed on effector/memory T cells and natural killer cells. Costimulatory signals received by T cells can impact both central and peripheral tolerance mechanisms. Genetic polymorphisms in CD226 have been associated with susceptibility to type 1 diabetes and other autoimmune diseases. We hypothesized that genetic deletion of Cd226 in the non-obese diabetic (NOD) mouse would impact type 1 diabetes incidence by altering T cell activation. CD226 knockout (KO) NOD mice displayed decreased disease incidence and insulitis in comparison to wild-type (WT) controls. Although female CD226 KO mice had similar levels of sialoadenitis as WT controls, male CD226 KO mice showed protection from dacryoadenitis. Moreover, CD226 KO T cells were less capable of adoptively transferring disease compared to WT NOD T cells. Of note, CD226 KO mice demonstrated increased CD8+ single positive (SP) thymocytes, leading to increased numbers of CD8+ T cells in the spleen. Decreased percentages of memory CD8+CD44+CD62L– T cells were observed in the pancreatic lymph nodes of CD226 KO mice. Intriguingly, CD8+ T cells in CD226 KO mice showed decreased islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-tetramer and CD5 staining, suggesting reduced T cell receptor affinity for this immunodominant antigen. These data support an important role for CD226 in type 1 diabetes development by modulating thymic T cell selection as well as impacting peripheral memory/effector CD8+ T cell activation and function.