The role of T-cells in the pathogenesis of Type 1 diabetes: From cause to cure View Full Text


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Article Info

DATE

2003-03-22

AUTHORS

Bart O. Roep

ABSTRACT

Type 1 diabetes mellitus results from a T-cell mediated autoimmune destruction of the pancreatic beta cells in genetically predisposed individuals. The knowledge of the immunopathogenesis has increased enormously in the last two decades. The contribution of T-cells in the pathogenesis is beyond doubt. Therapies directed against T-cells have been shown to halt the disease process and prevent recurrent beta-cell destruction after islet transplantation. Less is known about the nature and function of these T-cells, the cause of the loss of tolerance to islet autoantigens, why the immune system apparently fails to suppress autoreactivity, and whether (or which) autoantigen(s) are critically involved in the initiation or progression of the disease. The contribution of dendritic cells in directing the immune response is clear, while the contribution of B-cells and autoantibodies is subject to reconsideration. Autoreactive T-cells have proven to be valuable tools to study pathogenic or diabetes-related processes. Measuring T-cell autoreactivity has also provided critical information to determine the fate of islet allografts transplanted to Type 1 diabetic patients. Cellular autoimmunity is a difficult study subject, but it has been a worthwhile quest to unravel the role of T-cells in the pathogenesis of Type 1 diabetes. The challenge for the future is to determine which factors contribute to the loss of tolerance to beta-cell antigens, and to define what measures T-cells can provide to suppress autoreactivity, since it is becoming increasingly evident that T-cells provide a two-edged sword: some T-cells could be pathogenic, but others can regulate the disease process and thus form new targets for immunointervention. More... »

PAGES

305-321

References to SciGraph publications

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  • 1994-02. Lymphocyte subset abnormalities, autoantibodies and their relationship with HLA DR types in children with Type 1 (insulin-dependent) diabetes and their first degree relatives in DIABETOLOGIA
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  • 1995-01. HLA-matched control subjects are essential in studies of susceptibility to IDDM in DIABETOLOGIA
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  • 1997-02. T-cell reactivity to GAD65 peptide sequences shared with coxsackie virus protein in recent-onset IDDM, post-onset IDDM patients and control subjects in DIABETOLOGIA
  • 1990-06. T-cell clones from a type-1 diabetes patient respond to insulin secretory granule proteins in NATURE
  • 2001-04. Restoration of self-tolerance is a feasible approach to control ongoing beta-cell specific autoreactivity: its relevance for treatment in established diabetes and islet transplantation in DIABETOLOGIA
  • 1998-01. Extreme Th1 bias of invariant Vα24JαQ T cells in type 1 diabetes in NATURE
  • 1997-03. The insulin gene is transcribed in the human thymus and transcription levels correlate with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes in NATURE GENETICS
  • 1999-01. Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus in DIABETOLOGIA
  • 1997-04. Altered immune response to insulin in newly diagnosed compared to insulin-treated diabetic patients and healthy control subjects in DIABETOLOGIA
  • 1990-09. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase in NATURE
  • 1992-09. Early T-cell defects in pre-type 1 diabetes in ACTA DIABETOLOGICA
  • 2000-06. T-Cell markers in Type I diabetes: progress, prospects and realistic expectations in DIABETOLOGIA
  • 1999-09. Inhibition of insulin-specific autoreactive T-cells by sulphatide which is variably expressed in beta cells in DIABETOLOGIA
  • 1989-05. Persistent reduction of CD4/CD8 lymphocyte ratio amd cell activation before the onset of Type 1 (insulin-dependent) diabetes in DIABETOLOGIA
  • 1990-02. Examination of islets in the pancreas biopsy specimens from newly diagnosed Type 1 (insulin-dependent) diabetic patients in DIABETOLOGIA
  • 1999-03. Autoreactive and immunoregulatory T-cell subsets in insulindependent diabetes mellitus in DIABETOLOGIA
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    http://scigraph.springernature.com/pub.10.1007/s00125-003-1089-5

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    http://dx.doi.org/10.1007/s00125-003-1089-5

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/12687328


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