| Title | Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. | | Author(s) | Fife BT, Pauken KE, Eagar TN, Obu T, Wu J, Tang Q, Azuma M, Krummel MF, Bluestone JA | | Institution | [1] UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, California, USA. [2] Department of Medicine, Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA. | | Source | Nat Immunol 2009 Sep 27. | | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19783989 |
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