Association between αβTcR+CD4-CD8- T-cell deficiency and IDDM in NOD/Lt mice

Baxter, Alan G., Kinder, Simon J., Hammond, Kirsten J.L., Scollay, Roland, and Godfrey, Dale I. (1997) Association between αβTcR+CD4-CD8- T-cell deficiency and IDDM in NOD/Lt mice. Diabetes, 46 (4). pp. 572-582.

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Abstract

NOD mice develop spontaneous IDDM as a result of T-cell-mediated autoimmune destruction of pancreatic β-cells. It is not known why these T-cells become autoreactive, nor is it clear whether the breakdown in self-tolerance reflects a general problem in T-cell development or a selective defect in an as yet undefined regulatory cell population. In this study, we showed that NOD mice, although relatively normal with regard to most thymocyte subsets, exhibit a marked deficiency in αβTCR+CD4-CD8- (αβ+DN) T-cells in the thymus and, to a lesser extent, in the periphery. These T-cells have been termed NKT cells (NK1.1+-like T-cells) because they share some cell surface markers with conventional natural killer (NK) cells. To examine the role of these cells in the pathogenesis of IDDM, semiallogeneic or syngeneic double-negative (DN) thymocytes, enriched for NKT cells, were transferred into intact 4-week-old NOD recipients; the onset of diabetes was then monitored over the ensuing 30 weeks. Mice receiving NKT-enriched thymocytes did not develop diabetes, whereas mice receiving unfractionated thymocytes or phosphate-buffered saline developed diabetes at the normal rate. NKT cells represent a distinct T-cell lineage that has been shown to play a role in immunoregulation in vivo. The deficiency of these cells observed in NOD mice may therefore contribute to destruction of pancreatic islet cells by conventional T-cells.

Item ID: 8430
Item Type: Article (Refereed Research - C1)
ISSN: 0012-1797
Date Deposited: 07 Sep 2010 02:58
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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