Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4.
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.
Probst
Hans Christian
HC
Institute of Experimental Immunology, University Hospital Zurich, Switzerland.
McCoy
Kathy
K
Okazaki
Taku
T
Honjo
Tasuku
T
van den Broek
Maries
M
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D003713:Dendritic Cells / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D051379:Mice; D061026:Programmed Cell Death 1 Receptor
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor