title: A potential new pathway for PD-L1 costimulation of the CD8-T cell response to Listeria monocytogenes infection.
abstract: 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.
authors: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
authors: Daqi
authors: D
authors: Xu
authors: Han-Hsuan
authors: HH
authors: Fu
authors: Joshua J
authors: JJ
authors: Obar
authors: Jang-June
authors: JJ
authors: Park
authors: Koji
authors: K
authors: Tamada
authors: Hideo
authors: H
authors: Yagita
authors: Leo
authors: L
authors: Lefrançois
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D060890:B7-H1 Antigen / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000821:virology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation; D018116:Vesiculovirus / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D018984:Epitopes, T-Lymphocyte; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor