A potential new pathway for PD-L1 costimulation of the CD8-T cell response to Listeria monocytogenes infection

Programmed death ligand-1 (PD-L1) is an important negative regulator of T cell immune responses via interactions with PD-1 and CD80. However, PD-L1 can also act as a positive costimulator, but the relevant counterreceptor is not known. We analyzed the role of PD-L1 in CD8-T cell responses to infecti...

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Bibliographic Details
Published in:PloS one 2013-02, Vol.8 (2), p.e56539-e56539
Main Authors: Xu, Daqi, Fu, Han-Hsuan, Obar, Joshua J, Park, Jang-June, Tamada, Koji, Yagita, Hideo, Lefrançois, Leo
Format: Article
Language:English
Subjects:
Analysis
Animals
Antibodies, Monoclonal - immunology
Antigens
Antigens, Differentiation - immunology
Apoptosis
B cells
B7-1 Antigen - immunology
B7-H1 Antigen - immunology
B7-H1 Antigen - metabolism
Bacterial infections
Biology
Cancer
CD4 antigen
CD8 antigen
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
CD80 antigen
Cell Differentiation
Cell Proliferation
Cost analysis
Costimulator
Epitopes
Epitopes, T-Lymphocyte - immunology
Health aspects
Immune response
Immune response (cell-mediated)
Immunology
Infection
Infections
Ligands
Listeria
Listeria monocytogenes
Listeria monocytogenes - immunology
Listeriosis - immunology
Listeriosis - microbiology
Lymphocytes
Lymphocytes T
Medicine
Mice
Mice, Inbred C57BL
PD-1 protein
PD-L1 protein
Programmed Cell Death 1 Receptor
Rhabdoviridae Infections - immunology
Rhabdoviridae Infections - virology
Signal Transduction
Stomatitis
T cell receptors
T cells
T-Lymphocyte Subsets - cytology
T-Lymphocyte Subsets - immunology
Up-Regulation
Vaccines
Vesiculovirus - immunology
Viral infections
Viruses
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Summary:Programmed death ligand-1 (PD-L1) is an important negative regulator of T cell immune responses via interactions with PD-1 and CD80. However, PD-L1 can also act as a positive costimulator, but the relevant counterreceptor is not known. We analyzed the role of PD-L1 in CD8-T cell responses to infection with Listeria monocytogenes (LM) or vesicular stomatitis virus (VSV). PD-L1 blockade impaired antigen-specific CD8 effector T cell expansion in response to LM, but not to VSV infection, particularly limiting short-lived effector cell differentiation. Simultaneous CD4-T cell depletion and anti-PD-L1 blockade revealed that PD-L1 provided costimulation even in the absence of CD4-T cells. Most importantly, specific blockade of PD-L1 binding to CD80 or to PD-1 did not recapitulate PDL-1 blockade. The results suggested that PD-L1 plays an important costimulatory role for antigen-specific CD8 T cells during LM infection perhaps through a distinct receptor or interaction epitope.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0056539