Co-segregation of a gene encoding a deletion ligand for Tcrb-V3+ T cells with Mtv-3

Fairchild, Sue; Knight, Andrew M.; Dyson, Pamela; Tomonari, Kyuhei

doi:10.1007/bf00215257

Cited by 40 publications

(27 citation statements)

References 29 publications

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“…Hence though C57BL/ 10 mice have been categorized as Mtv-30 negative [15,17], B10.BR mice have been found to be Mtv-30 positive [33]. As the definition of C57BL/10 mice as Mtv-30 negative in fact appears to derive from an analysis of B10.BR DNA [34], the existing data are contradictory. In fact, surprisingly, we can find no report in which C57BL/10 mice have been Mtv typed.…”

Section: Chronic Deletion Of Mtv Sag-reactive T Cellsmentioning

confidence: 88%

Chronic deletion, escape from deletion and activation of mouse mammary tumor virus superantigen-reactive T cells in C57BL/10 mice

Dyson

Elliott

1999

Eur. J. Immunol.

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Though C57BL/10 mice express the mouse mammary tumor virus superantigens (sag) encoded by Mtv-8 and Mtv-9, it has been thought that these sag do not bind to the MHC class II molecule H2-Ab and consequently do not affect the T cell repertoire. However, we show that cells bearing TCR Vbeta chains specific for Mtv-8 and -9 sag are chronically deleted in C57BL/10 mice. Thymocytes and peripheral T cells escaping deletion by Mtv sag display a small reduction in the level of cell surface CD4. T cells escaping thymic deletion respond variably to endogenous Mtv sag with some, but not all, reactive populations appearing overrepresented in the activated/memory subset. The data suggest that in normal mice fine modulation of coreceptor expression levels may be a common way by which thymocytes escape elimination, that systems utilizing potentially Mtv sag-reactive TCR on a C57BL background may be inappropriate for the measurement of the affinity of TCR/MHC/peptide interactions required in thymic selection, and that detection of the activity of human sag may be aided by analysis of CD4 levels and activation markers on T cells in conjunction with studies of the frequency of cells bearing specific TCRVbeta chains.

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Section: Chronic Deletion Of Mtv Sag-reactive T Cellsmentioning

confidence: 88%

Chronic deletion, escape from deletion and activation of mouse mammary tumor virus superantigen-reactive T cells in C57BL/10 mice

Dyson

Elliott

1999

Eur. J. Immunol.

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“…To test this hypothesis, we made use of differences in superantigen-mediated deletion of informative V␤ subsets between the AKR and NOD strains (reviewed in 18). AKR mice delete V␤6 and other V␤ families, whereas NOD mice delete V␤3 ϩ cells (19). Thus, as shown in Table 2).…”

Section: Effect Of Hct On Insulitismentioning

confidence: 90%

Purified Allogeneic Hematopoietic Stem Cell Transplantation Blocks Diabetes Pathogenesis in NOD Mice

et al. 2003

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Purified hematopoietic stem cells (HSCs) were transplanted into NOD mice to test whether development of hyperglycemia could be prevented. Engraftment of major histocompatibility complex-mismatched HSCs was compared with bone marrow (BM) grafts. HSCs differed from BM because HSCs were more strongly resisted and HSC recipients retained significant levels of NOD Tcells, whereas BM recipients were full donor chimeras. Despite persistent NOD T-cells, all HSC chimeras were protected from hyperglycemia, and attenuation of islet lesions was observed. T-cell selection was altered in allogeneic HSC recipients as demonstrated by deletion of both donor and host superantigen-specific T-cells. Syngeneic and congenic hematopoietic cell transplants were also performed to differentiate the influence of the preparative regimen(s) versus the allografts. Unlike the allogeneic HSC transplantations, syngeneic or congenic grafts did not retard diabetes development. In a pilot study, overtly diabetic NOD mice were cured by cotransplantation of allogeneic HSCs and donor-matched islets. We conclude that allogeneic HSC transplants block allo-and autoimmunity, despite residual host T-cell presence. These data demonstrate for the first time that purified HSC grafts block development of autoimmune diabetes and illuminate how HSC grafts alter thymic and peripheral T-cell responses against auto-and alloantigens. Diabetes 52:59 -68, 2003

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“…NOD mice harbor an endogenous murine mammary tumor virus (Mtv)-3-encoded superantigen (SAg) that deletes the vast majority of V␤3 ϩ thymocytes (28). Thus, these results suggested that rare NOD T cells that escape deletion may become activated and contribute to the early stages of autoimmune islet infiltration.…”

Section: Genetic Control Of T and B Lymphocyte Activation Inmentioning

confidence: 99%

Genetic Control of T and B Lymphocyte Activation in Nonobese Diabetic Mice

Chiu

Jevnikar

Danska

2001

The Journal of Immunology

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Type 1 diabetes in nonobese diabetic (NOD) mice is characterized by the infiltration of T and B cells into pancreatic islets. T cells bearing the TCR Vβ3 chain are disproportionately represented in the earliest stages of islet infiltration (insulitis) despite clonal deletion of most Vβ3+ immature thymocytes by the mammary tumor virus-3 (Mtv-3) superantigen (SAg). In this report we showed that a high frequency of NOD Vβ3+ T cells that escape deletion are activated in vivo and that this phenotype is linked to the Mtv-3 locus. One potential mechanism of SAg presentation to peripheral T cells is by activated B cells. Consistent with this idea, we found that NOD mice harbor a significantly higher frequency of activated B cells than nondiabetes-prone strains. These activated NOD B cells expressed cell surface molecules consistent with APC function. At the molecular level, the IgH repertoire of activated B cells in NOD mice was equivalent to resting B cells, suggesting a polyclonal response in vivo. Genetic analysis of the activated B cell phenotype showed linkage to Idd1, the NOD MHC haplotype (H-2g7). Finally, Vβ3+ thymocyte deletion and peripheral T cell activation did not require B cells, suggesting that other APC populations are sufficient to generate both Mtv-3-linked phenotypes. These data provide insight into the genetic regulation of NOD autoreactive lymphocyte activation that may contribute to failure of peripheral tolerance and the pathogenesis of type I diabetes.

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Co-segregation of a gene encoding a deletion ligand for Tcrb-V3+ T cells with Mtv-3

Cited by 40 publications

References 29 publications

Chronic deletion, escape from deletion and activation of mouse mammary tumor virus superantigen-reactive T cells in C57BL/10 mice

Chronic deletion, escape from deletion and activation of mouse mammary tumor virus superantigen-reactive T cells in C57BL/10 mice

Purified Allogeneic Hematopoietic Stem Cell Transplantation Blocks Diabetes Pathogenesis in NOD Mice

Genetic Control of T and B Lymphocyte Activation in Nonobese Diabetic Mice

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