Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade
Open Access
- 26 September 2011
- journal article
- Published by Springer Science and Business Media LLC in Veterinary Research
- Vol. 42 (1), 103
- https://doi.org/10.1186/1297-9716-42-103
Abstract
The inhibitory receptor programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1) are involved in immune evasion mechanisms for several pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores anti-virus immune responses, with concomitant reduction in viral load. In a previous report, we showed that, in bovine leukemia virus (BLV) infection, the expression of bovine PD-1 is closely associated with disease progression. However, the functions of bovine PD-L1 are still unknown. To investigate the role of PD-L1 in BLV infection, we identified the bovine PD-L1 gene, and examined PD-L1 expression in BLV-infected cattle in comparison with uninfected cattle. The deduced amino acid sequence of bovine PD-L1 shows high homology to the human and mouse PD-L1. The proportion of PD-L1 positive cells, especially among B cells, was upregulated in cattle with the late stage of the disease compared to cattle at the aleukemic infection stage or uninfected cattle. The proportion of PD-L1 positive cells correlated positively with prediction markers for the progression of the disease such as leukocyte number, virus load and virus titer whilst on the contrary, it inversely correlated with the degree of interferon-gamma expression. Blockade of the PD-1/PD-L1 pathway in vitro by PD-L1-specific antibody upregulated the production of interleukin-2 and interferon-gamma, and correspondingly, downregulated the BLV provirus load and the proportion of BLV-gp51 expressing cells. These data suggest that PD-L1 induces immunoinhibition in disease progressed cattle during chronic BLV infection. Therefore, PD-L1 would be a potential target for developing immunotherapies against BLV infection.Keywords
This publication has 35 references indexed in Scilit:
- Programmed death (PD)-1 molecule and its ligand PD-L1 distribution among memory CD4 and CD8 T cell subsets in human immunodeficiency virus-1-infected individualsClinical and Experimental Immunology, 2009
- Enhancing SIV-specific immunity in vivo by PD-1 blockadeNature, 2008
- Human Immunodeficiency Virus Type 1 Nef Induces Programmed Death 1 Expression through a p38 Mitogen-Activated Protein Kinase-Dependent MechanismJournal of Virology, 2008
- Selective expansion of a subset of exhausted CD8 T cells by αPD-L1 blockadeProceedings of the National Academy of Sciences of the United States of America, 2008
- Antigen Load and Viral Sequence Diversification Determine the Functional Profile of HIV-1–Specific CD8+ T CellsPLoS Medicine, 2008
- B7-H1 is a ubiquitous antiapoptotic receptor on cancer cellsBlood, 2008
- PD-1 and Its Ligands in Tolerance and ImmunityAnnual Review of Immunology, 2008
- Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell ResponsesImmunity, 2007
- Characterization of Hepatitis B Virus (HBV)-Specific T-Cell Dysfunction in Chronic HBV InfectionJournal of Virology, 2007
- PD-1 Expression in Acute Hepatitis C Virus (HCV) Infection Is Associated with HCV-Specific CD8 ExhaustionJournal of Virology, 2006