Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal.
Nat Immunol
; 10(11): 1185-92, 2009 Nov.
Article
in En
| MEDLINE
| ID: mdl-19783989
ABSTRACT
Programmed death 1 (PD-1) is an inhibitory molecule expressed on activated T cells; however, the biological context in which PD-1 controls T cell tolerance remains unclear. Using two-photon laser-scanning microscopy, we show here that unlike naive or activated islet antigen-specific T cells, tolerized islet antigen-specific T cells moved freely and did not swarm around antigen-bearing dendritic cells (DCs) in pancreatic lymph nodes. Inhibition of T cell antigen receptor (TCR)-driven stop signals depended on continued interactions between PD-1 and its ligand, PD-L1, as antibody blockade of PD-1 or PD-L1 resulted in lower T cell motility, enhanced T cell-DC contacts and caused autoimmune diabetes. Blockade of the immunomodulatory receptor CTLA-4 did not alter T cell motility or abrogate tolerance. Thus, PD-1-PD-L1 interactions maintain peripheral tolerance by mechanisms fundamentally distinct from those of CTLA-4.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Membrane Glycoproteins
/
Receptors, Antigen, T-Cell
/
Signal Transduction
/
B7-1 Antigen
/
Apoptosis Regulatory Proteins
/
Immune Tolerance
/
Antigens, Surface
Limits:
Animals
Language:
En
Journal:
Nat Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2009
Type:
Article
Affiliation country:
United States