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Differentiating MHC-Dependent and -Independent Mechanisms of Lymph Node Stromal Cell Regulation of Proinsulin-Specific CD8 + T Cells in Type 1 Diabetes.
- Source :
-
Diabetes [Diabetes] 2021 Feb; Vol. 70 (2), pp. 529-537. Date of Electronic Publication: 2020 Oct 29. - Publication Year :
- 2021
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Abstract
- Lymph node stromal cells (LNSC) are essential for providing and maintaining peripheral self-tolerance of potentially autoreactive cells. In type 1 diabetes, proinsulin-specific CD8 <superscript>+</superscript> T cells, escaping central and peripheral tolerance, contribute to β-cell destruction. Using G9Cα <superscript>-/-</superscript> CD8 <superscript>+</superscript> T cells specific for proinsulin, we studied the mechanisms by which LNSC regulate low-avidity autoreactive cells in the NOD mouse model of type 1 diabetes. Whereas MHC-matched NOD-LNSC significantly reduced G9Cα <superscript>-/-</superscript> CD8 <superscript>+</superscript> T-cell cytotoxicity and dendritic cell-induced proliferation, they failed to sufficiently regulate T cells stimulated by anti-CD3/CD28. In contrast, non-MHC-matched, control C57BL/6 mouse LNSC suppressed T-cell receptor engagement by anti-CD3/CD28 via MHC-independent mechanisms. This C57BL/6-LNSC suppression was maintained even after removal of the LNSC, demonstrating a direct effect of LNSC on T cells, modifying antigen sensitivity and effector function. Thus, our results suggest that a loss of NOD-LNSC MHC-independent suppressive mechanisms may contribute to diabetes development.<br /> (© 2020 by the American Diabetes Association.)
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 70
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 33122391
- Full Text :
- https://doi.org/10.2337/db19-1050