Flow Cytometric Study of T Cell Development in NOD Mice Reveals a Deficiency in αβTCR+CD4−CD8−Thymocytes

Godfrey, Dale I.; Kinder, Simon J.; Silvera, Pablo; Baxter, Alan G.

doi:10.1006/jaut.1997.0129

Cited by 92 publications

(81 citation statements)

References 22 publications

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“…1B]) and ␣␤-TCR ϩ CD4 Ϫ CD8 Ϫ subset, which contains regulatory NKT cells. This latter deficiency has been reported previously (10,21) and will be discussed further.…”

Section: Resultssupporting

confidence: 80%

“…Thymic abnormalities reported to affect NOD mice include structural irregularities (9), accumulations and deficiencies of particular thymocyte subsets (10), and export dysregulation (4), yet the size and distribution of NOD thymocyte subsets is generally observed to be normal (21). In light of this apparent inconsistency and the recent suggestion of defective negative selection (12), we compared the size and relative proportions of different thymocyte subsets in prediabetic NOD mice versus control (nonautoimmune) strains.…”

Section: Resultsmentioning

confidence: 99%

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T-Cell Compartments of Prediabetic NOD Mice

et al. 2003

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Given the importance of the NOD mouse as a model of type 1 diabetes, there is a surprising lack of published information on the overall composition of the thymic and peripheral T-cell compartments. In this study, we revisited some earlier reports of T-cell abnormalities in this strain and examined a number of additional parameters to provide a global view of T-cells in prediabetic NOD mice. In some cases, we concur with past conclusions, but in other important areas, we find that NOD mice closely resemble nonautoimmune strains. Specifically, and contrary to published reports, the thymocyte subset distribution, the rate and composition of thymic export, and the composition of the peripheral T-cell pool, including the proportion of CD25 ؉ CD4 ؉ T-cells, are essentially normal in prediabetic NOD mice. These factors are therefore unlikely to be involved in the loss of tolerance that leads to autoimmunity within this strain. Diabetes 52:327-334, 2003

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“…1B]) and ␣␤-TCR ϩ CD4 Ϫ CD8 Ϫ subset, which contains regulatory NKT cells. This latter deficiency has been reported previously (10,21) and will be discussed further.…”

Section: Resultssupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

T-Cell Compartments of Prediabetic NOD Mice

et al. 2003

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“…ϩ CD25 ϩ T-cells were present in VDR Ϫ/Ϫ NOD immune organs, postulated to contribute to an inability to maintain peripheral tolerance and, hence, diabetes development in NOD mice (20,21). Moreover, inactivation of VDR in NOD mice resulted in disturbed cytokine and chemokine profile with extremely low IL-1, IL-6, and CCL2 transcripts, implicated in aberrant migratory capacity, possibly trapping the macrophages in the pancreas and leading to nonspecific damage of ␤-cells (22).…”

Section: Discussionmentioning

confidence: 99%

Unaltered Diabetes Presentation in NOD Mice Lacking the Vitamin D Receptor

et al. 2008

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OBJECTIVE-Vitamin include modulation of phenotype and function of dendritic cells, restoration of regulatory T cells, and improved elimination of autoimmune effector cells (9). 1,25(OH) 2 D 3 acts via the vitamin D receptor (VDR), which belongs to the steroid hormone receptor superfamily. As VDR is expressed in ␤-cells and in most immune cells, it is not surprising that the 1,25(OH) 2 D 3 -VDR complex modulates insulin secretion, cell differentiation, and innate and adaptive immune functions. Moreover, associations between some VDR polymorphisms and type 1 diabetes have been described in several populations (10,11). In view of these data, we investigated the role of the VDR gene in autoimmune diabetes development by generating and studying a congenic stock of NOD mice with a disruption of the VDR gene. RESEARCH DESIGN AND METHODSThe original Vdr tm1Ska /Vdr tm1Ska (VDR Ϫ/Ϫ ) mice were produced by Dr. S. Kato (University of Tokyo, Tokyo, Japan) and were kept on C57BL/6 ϫ CBA background (12). After backcrossing male VDR Ϫ/ϩ heterozygotes to female NOD mice (N10 and N14), VDR Ϫ/ϩ NOD mice were intercrossed to produce experimental animals of three genotypes. Genotypes of mice from N2 to N14 generation were determined by testing tail DNA with microsatellite markers linked to 15 insulin-dependent diabetes loci (Idd1-Idd15), as previously described (13).All experiments were performed on age-and sex-matched VDR Ϫ/Ϫ and VDR ϩ/ϩ NOD littermates from intercrosses of N10 and N14 generations. Complete methods, including a description of the procedures for all in vitro immune phenotyping, assessment of diabetes, pancreatic histopathology with insulitis scoring and insulin content determination, calcium and bone parameters, RNA isolation, and quantitative RT-PCR analysis are provided in an online appendix (available at http://dx.doi.org/10.2337/db07-1095).Data were analyzed using NCSS 2000 statistical software (Kaysville, UT). Results are expressed as means Ϯ SEM, and differences are considered significant when P Յ 0.05. Differences between groups were evaluated by ANOVA and post hoc unpaired Student's t test. For comparing the in vivo insulitis and diabetes incidence, Kaplan-Meier survival curves, the log-rank test, and the 2 test were used.From the

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“…Activation of type I NKT cells with ␣GalCer protected mice from autoimmune type I diabetes mellitus (82), and NOD mice that are diabetes-prone appeared to have substantially lower NKT numbers (83,84). Moreover, reconstitution of NKT cells by adoptive transfer protected NOD mice against diabetes in a IL-4-and IL-10-dependent manner (85,86), although the mechanism of protection is still controversial (87).…”

Section: Regulatory Role Of Type I Nkt Cells In Autoimmunity Andmentioning

confidence: 99%