Journal article
CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation
Frontiers in immunology, Vol.11, pp.2180-2180
09/04/2020
DOI: 10.3389/fimmu.2020.02180
PMCID: PMC7500101
PMID: 33013915
Abstract
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 inCD226have been associated with susceptibility to type 1 diabetes and other autoimmune diseases. We hypothesized that genetic deletion ofCd226in 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.
Details
- Title: Subtitle
- CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation
- Creators
- Melanie R. Shapiro - University of FloridaWen Yeh - University of FloridaJoshua R. Longfield - University of FloridaJohn Gallagher - University of FloridaCaridad M. Infante - University of FloridaSarah Wellford - University of FloridaAmanda L. Posgai - University of FloridaMark A. Atkinson - University of FloridaMartha Campbell-Thompson - University of FloridaScott M. Lieberman - University of IowaDavid V. Serreze - Jackson LaboratoryAron M. Geurts - Medical College of WisconsinYi-Guang Chen - Medical College of WisconsinTodd M. Brusko - University of Florida
- Resource Type
- Journal article
- Publication Details
- Frontiers in immunology, Vol.11, pp.2180-2180
- DOI
- 10.3389/fimmu.2020.02180
- PMID
- 33013915
- PMCID
- PMC7500101
- NLM abbreviation
- Front Immunol
- ISSN
- 1664-3224
- eISSN
- 1664-3224
- Publisher
- Frontiers Media Sa
- Number of pages
- 13
- Grant note
- F31 DK117548; R01 EY027731; DP3 DK097605; PO1 AI42288; R01 DK107541; R01 DK106191; R01 DK46266; DK95735 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 1-16-PDF-131 / American Diabetes Association fellowship; American Diabetes Association
- Language
- English
- Date published
- 09/04/2020
- Academic Unit
- Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
- Record Identifier
- 9984353830102771
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