Programmed cell death 1 (PD-1) and its ligand PD-L1 are required for allograft tolerance

✍ Scribed by Liqing Wang; Rongxiang Han; Wayne W. Hancock

• Book ID: 102167516
• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 429 KB
• Volume: 37
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200737583

✦ Synopsis

Abstract

Programmed cell death‐1 (PD‐1, CD279) and its widely expressed, inducible ligand, PD‐L1 (CD274), together dampen T cell activation, but whether they are essential for allograft tolerance is unknown. We show, using gene‐deficient mice and blocking mAbs in wild‐type mice, that costimulation blockade is ineffectual in PD‐1^–/–^ or PD‐L1^–/–^ allograft recipients, or in wild‐type allograft recipients treated with anti‐PD‐1 or anti‐PD‐L1 mAb. Alloreactive PD‐1^–/–^ CD4 and CD8 T cells had enhanced proliferation and cytokine production compared to wild‐type controls, and anergy could not be induced in PD‐1‐deficient CD4 T cells. We conclude that without inhibitory signals from PD‐1 ligation, alloantigen‐induced T cell proliferation and expansion cannot be regulated by costimulation blockade, and peripheral tolerance induction cannot occur.