PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing

Ilseyar Akhmetzyanova, Malgorzata Drabczyk, C. Preston Neff, Kathrin Gibbert, Kirsten K. Dietze, Tanja Werner, Jia Liu, Lieping Chen, Karl S. Lang, Brent E. Palmer, Ulf Dittmer, Gennadiy Zelinskyy

Research output: Contribution to journalArticle

Abstract

Cytotoxic CD8+ T Lymphocytes (CTL) efficiently control acute virus infections but can become exhausted when a chronic infection develops. Signaling of the inhibitory receptor PD-1 is an important mechanism for the development of virus-specific CD8+ T cell dysfunction. However, it has recently been shown that during the initial phase of infection virus-specific CD8+ T cells express high levels of PD-1, but are fully competent in producing cytokines and killing virus-infected target cells. To better understand the role of the PD-1 signaling pathway in CD8+ T cell cytotoxicity during acute viral infections we analyzed the expression of the ligand on retrovirus-infected cells targeted by CTLs. We observed increased levels of PD-L1 expression after infection of cells with the murine Friend retrovirus (FV) or with HIV. In FV infected mice, virus-specific CTLs efficiently eliminated infected target cells that expressed low levels of PD-L1 or that were deficient for PD-L1 but the population of PD-L1high cells escaped elimination and formed a reservoir for chronic FV replication. Infected cells with high PD-L1 expression mediated a negative feedback on CD8+ T cells and inhibited their expansion and cytotoxic functions. These findings provide evidence for a novel immune escape mechanism during acute retroviral infection based on PD-L1 expression levels on virus infected target cells.

Original languageEnglish (US)
Article numbere1005224
JournalPLoS Pathogens
Volume11
Issue number10
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

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  • Cite this

    Akhmetzyanova, I., Drabczyk, M., Neff, C. P., Gibbert, K., Dietze, K. K., Werner, T., Liu, J., Chen, L., Lang, K. S., Palmer, B. E., Dittmer, U., & Zelinskyy, G. (2015). PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing. PLoS Pathogens, 11(10), [e1005224]. https://doi.org/10.1371/journal.ppat.1005224