Gj. Freeman et al., Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation, J EXP MED, 192(7), 2000, pp. 1027-1034
PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cell
s, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of periphe
ral tolerance and demonstrate multiple autoimmune features. We report here
that the ligand of PD-1 (PD-LI) is a member of the B7 gene family. Engageme
nt of PD-1 by PD-L1 leads to the inhibition of T cell rcceptor-mediated lym
phocyte proliferation and cytokine secretion. In addition, PD-1 signaling c
an inhibit at least suboptimal levels of CD28-mediated costimulation. PD-L1
is expressed by antigen-presenting cells, including human peripheral blood
monocytes stimulated with interferon gamma, and activated human and murine
dendritic cells. In addition, PD-L1 is expressed in nonlymphoid tissues su
ch as heart and lung. The relative levels of inhibitory PD-L1 and costimula
tory B7-1/B7-2 signals on antigen-presenting cells may determine the extent
of T cell activation and consequently the threshold between tolerance and
autoimmunity. PD-L1 expression on nonlymphoid tissues and its potential int
eraction with PD-1 may subsequently determine the extent of immune response
s at sites of inflammation.