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.
Association Between αβTCR+CD4−CD8− T-Cell Deficiency and IDDM in NOD/Lt Mice
ANOVA, analysis of variance; CFA, complete Freund's adjuvant; DN, double-negative; DP, double-positive; FACS, fluorescence-activated cell sorter; FITC, fluorescein isothiocyanate; HSA, heat stable antigen; ISP, immature single-positive; mAb, monoclonal antibody; MHC, major histocompatibility complex; NK cell, natural killer cell; NKT cells, NK1.1+ -like T-cells; PBS, phosphate-buffered saline; PE, phycoerythrin; SP, single-positive; TCR, T-cell receptor.
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Alan G Baxter, Simon J Kinder, Kirsten J L Hammond, Roland Scollay, Dale I Godfrey; Association Between αβTCR+CD4−CD8− T-Cell Deficiency and IDDM in NOD/Lt Mice. Diabetes 1 April 1997; 46 (4): 572–582. https://doi.org/10.2337/diab.46.4.572
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