Transgenic Ly-49A inhibits antigen-driven T cell activation and delays diabetes.
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-2D(d), 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.
Smith
Sherry S
SS
Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield 62702, USA.
Patterson
Tricia
T
Pauza
Mary E
ME
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000950:Antigens, Ly / Q000235:genetics / Q000494:pharmacology*; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007376:Interleukin-2 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D055630:Receptors, NK Cell Lectin-Like
D000950:Antigens, Ly; D001324:Autoantigens; D016207:Cytokines; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007376:Interleukin-2; D037181:Lectins, C-Type; D055630:Receptors, NK Cell Lectin-Like