Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity

نویسندگان

  • Kristine M. Garza
  • Steven M. Chan
  • Rakesh Suri
  • Linh T. Nguyen
  • Bernhard Odermatt
  • Stephen P. Schoenberger
  • Pamela S. Ohashi
چکیده

The mechanisms that determine whether receptor stimulation leads to lymphocyte tolerance versus activation remain poorly understood. We have used rat insulin promoter (RIP)-gp/P14 double-transgenic mice expressing the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) on pancreatic beta-islet cells together with T cells expressing an LCMV-gp-specific T cell receptor to assess the requirements for the induction of autoimmunity. Our studies have shown that administration of the gp peptide gp33 leads to the activation of P14-transgenic T cells, as measured by the upregulation of activation markers and the induction of effector cytotoxic activity. This treatment also leads to expansion and deletion of P14 T cells. Despite the induction of cytotoxic T lymphocyte activity, peptide administration is not sufficient to induce diabetes. However, the administration of gp peptide together with an activating anti-CD40 antibody rapidly induces diabetes. These findings suggest that the induction of tolerance versus autoimmunity is determined by resting versus activated antigen-presenting cells.

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عنوان ژورنال:
  • The Journal of Experimental Medicine

دوره 191  شماره 

صفحات  -

تاریخ انتشار 2000