Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4

Nat Immunol. 2005 Mar;6(3):280-6. doi: 10.1038/ni1165. Epub 2005 Jan 30.


T cells recognizing self proteins exist without causing autoimmunity in healthy individuals. These autoreactive T cells are kept in check by peripheral tolerance. Using a model for peripheral CD8(+) T cell tolerance resulting from antigen presentation by resting dendritic cells in vivo, we show here that CD8(+) T cell tolerance operates through T cell-intrinsic mechanisms such as deletion or functional inactivation. Peripheral CD8(+) T cell tolerance depended on signaling via the costimulatory molecule PD-1, as an absence of PD-1 converted tolerance induction into priming. Blocking of the costimulatory molecule CTLA-4 resulted in impaired tolerance and enhanced the effect of the absence of PD-1, suggesting that PD-1 and CTLA-4 act synergistically. Thus PD-1 and CTLA-4 are crucial molecules for peripheral CD8(+) T cell tolerance induced by resting dendritic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD
  • Antigens, Differentiation / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen
  • Dendritic Cells / immunology*
  • Immune Tolerance* / immunology
  • Mice
  • Programmed Cell Death 1 Receptor


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor