Regulation of T cell activation and tolerance by PDL2.
T cell activation and tolerance are regulated by costimulatory molecules. Although PD-1 serves as a crucial negative regulator of T cells, the function of its ligands, PDL1 and PDL2, is still controversial. In this study, we created a PDL2-deficient mouse to characterize its function in T cell activation and tolerance. Antigen-presenting cells from PDL2-/- mice were found to be more potent in activation of T cells in vitro over the wild-type controls, which depended on PD-1. Upon immunization with chicken ovalbumin, PDL2-/- mice exhibited increased activation of CD4(+) and CD8(+) T cells in vivo when compared with WT animals. In addition, T cell tolerance to an oral antigen was abrogated by the lack of PDL2. Our results thus demonstrate that PDL2 negatively regulates T cells in immune responses and plays an essential role in immune tolerance.
Zhang
Yongliang
Y
Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Chung
Yeonseok
Y
Bishop
Caroline
C
Daugherty
Betsy
B
Chute
Hilary
H
Holst
Paige
P
Kurahara
Carole
C
Lott
Fred
F
Sun
Ning
N
Welcher
Andrew A
AA
Dong
Chen
C
D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology; D002645:Chickens; D007108:Immune Tolerance / Q000502:physiology*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D013601:T-Lymphocytes / Q000276:immunology*
D000943:Antigens, Differentiation; D008024:Ligands; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D010047:Ovalbumin