17924994

pubmed:Citation

12

Programmed death-1 (PD-1) is a recently identified coinhibitory molecule that belongs to the CD28 superfamily. PD-1 has two ligands PD-L1 and PD-L2. There is some evidence that PD-L1 and PD-L2 serve distinct functions, but their exact function in alloimmunity remains unclear. In the present study, we used a GVHD-like model that allows detailed analyses of T-cell activation at a single cell level in vivo to examine the role of PD-1/PD-L1 and PD-1/PD-L2 interactions in regulating proliferation of CD4(+) and CD8(+) T cells in response to alloantigen stimulation. We found that both CD4(+) and CD8(+) T cells proliferated vigorously in vivo and that PD-L1 and PD-L2 exhibit strikingly different effect on T-cell proliferation. While blocking PD-L1 did not affect the in vivo proliferation of CD4(+) and CD8(+) T cells regardless of CD28 costimulation, blocking PD-L2 resulted in a marked increase in the responder frequency of CD8(+) T-cells in vivo. The effect of PD-L2 on the CD8(+) T-cell proliferation is regulated by CD28 costimulation and by the CD4(+) T cells. We conclude that PD-L1 and PD-L2 function differently in regulating alloreactive T-cell activation in vivo, and PD-L2 is predominant in this model in limiting alloreactive CD8(+) T-cell proliferation.

eng

IM

MEDLINE

1600-6135

Print

NLM

2683-92

pubmed-meshheading:17924994-Animals, pubmed-meshheading:17924994-Antibodies, Monoclonal, pubmed-meshheading:17924994-Antigens, CD274, pubmed-meshheading:17924994-Antigens, CD28, pubmed-meshheading:17924994-Antigens, CD80, pubmed-meshheading:17924994-Apoptosis, pubmed-meshheading:17924994-CD4-Positive T-Lymphocytes, pubmed-meshheading:17924994-CD8-Positive T-Lymphocytes, pubmed-meshheading:17924994-Cell Proliferation, pubmed-meshheading:17924994-Disease Models, Animal, pubmed-meshheading:17924994-Graft vs Host Disease, pubmed-meshheading:17924994-Isoantigens, pubmed-meshheading:17924994-Membrane Glycoproteins, pubmed-meshheading:17924994-Mice, pubmed-meshheading:17924994-Mice, Inbred C57BL, pubmed-meshheading:17924994-Mice, Inbred DBA, pubmed-meshheading:17924994-Mice, Knockout, pubmed-meshheading:17924994-Peptides, pubmed-meshheading:17924994-Programmed Cell Death 1 Ligand 2 Protein, pubmed-meshheading:17924994-Signal Transduction

Striking dichotomy of PD-L1 and PD-L2 pathways in regulating alloreactive CD4(+) and CD8(+) T cells in vivo.

Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural