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.
Highlights
Optimal T cell activation requires three signals: 1) interaction between TCR and the cognate peptide-MHC complex, 2) positive costimulation of antigen-specific T cells to promote expansion and survival [1]; and 3) cytokines that facilitate T cell differentiation, expansion, and survival [2]
We investigated the role of Programmed death ligand-1 (PD-L1) in the regulation of the endogenous antigen-specific CD8 and CD4 T cell responses to bacteria and virus infections
We examined PD-L1 expression after i.v. infection with Listeria monocytogenes (LM)-ova or vesicular stomatitis virus (VSV)-ova
Summary
Optimal T cell activation requires three signals: 1) interaction between TCR and the cognate peptide-MHC complex, 2) positive costimulation of antigen-specific T cells to promote expansion and survival [1]; and 3) cytokines that facilitate T cell differentiation, expansion, and survival [2]. The pMHCI tetramer-OVA257–264/Kb was used to identify antigen-specific CD8 T cells on day 8 post LM-ova or day 7 post-VSV-ova infections, near the peak of the responses. The VSV-specific CD8 T cell response was not affected by either anti-PD-L1, –PD-L2, or -PD-1 mAbs (Fig. 2A and data not shown).
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