Transgenic Ly-49A inhibits antigen-driven T cell activation and delays diabetes
Autor: | Tricia Patterson, Sherry S. Smith, Mary E. Pauza |
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Rok vydání: | 2005 |
Předmět: |
CD4-Positive T-Lymphocytes
medicine.medical_specialty Receptor expression T cell Immunology Mice Transgenic Biology Lymphocyte Activation Autoantigens Interleukin 21 Islets of Langerhans Mice Internal medicine medicine Immunology and Allergy Cytotoxic T cell Animals Antigens Ly Lectins C-Type IL-2 receptor Antigen-presenting cell Histocompatibility Antigen H-2D Antigen Presentation ZAP70 H-2 Antigens CD28 Adoptive Transfer Cell biology Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 1 Cytokines Interleukin-2 Receptors NK Cell Lectin-Like |
Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 174(7) |
ISSN: | 0022-1767 |
Popis: | Activation of islet-specific T cells plays a significant role in the development of type 1 diabetes. In an effort to control T cell activation, we expressed the inhibitory receptor, Ly-49A, on islet-specific mouse CD4 cells. Ag-mediated activation of Ly-49A T cells was inhibited in vitro when the Ly-49A ligand, H-2Dd, was present on APCs. Ag-driven T cell proliferation, cytokine production, and changes in surface receptor expression were significantly reduced. Inhibition was also evident during secondary antigenic challenge. Addition of exogenous IL-2 did not rescue cells from inhibition, suggesting that Ly-49A engagement does not lead to T cell anergy. Importantly, in an adoptive transfer model, Ly-49A significantly delays the onset of diabetes. Together these results demonstrate that the inhibitory receptor Ly-49A effectively limits Ag-specific CD4 cell responses even in the presence of sustained autoantigen expression in vivo. |
Databáze: | OpenAIRE |
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