PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells.
PD-L1 and PD-L2 are ligands for PD-1, a costimulatory molecule that plays an inhibitory role in regulating T cell activation in the periphery. We find that PD-L1 is highly expressed on inflammatory macrophages as compared with resident peritoneal macrophages but can be induced on resident macrophages by classical activation stimuli such as lipopolysaccharide, IFN-gamma, and polyinosinic-polycytidylic acid. Further up-regulation of PD-L1 on inflammatory macrophages can also be induced by subsequent exposure to lipopolysaccharide and IFN-gamma. In contrast, PD-L2 is not expressed on inflammatory macrophages but can be induced by alternative activation via IL-4. Although PD-L1 is highly inducible on a variety of antigen-presenting cell lines as well as resident macrophages, PD-L2 is most significantly inducible only on inflammatory macrophages. PD-L1 up-regulation depends on TLR4 and STAT1, whereas PD-L2 expression depends on IL-4R alpha and STAT6. Consistent with these results, T helper 1T helper 2 (Th1/Th2) cells also differentially up-regulate PD-L1 and PD-L2 expression on inflammatory macrophages. Hence, Th1 cells as well as microbial products can enhance PD-L1 expression on many different macrophage populations, whereas Th2 cells instruct only inflammatory macrophages to up-regulate PD-L2. These results suggest that PD-L1 and PD-L2 might have different functions in regulating type 1 and type 2 responses.
Loke
P'ng
P
Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
Allison
James P
JP
D000595:Amino Acid Sequence; D000818:Animals; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000235:genetics*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D019948:Receptors, Interleukin-4 / Q000502:physiology; D050800:STAT6 Transcription Factor; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators