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

PLoS Pathogens

Karl S. Lang¹  Lieping Chen²  Brent E. Palmer³  Ilseyar Akhmetzyanova⁴  Tanja Werner⁴  Malgorzata Drabczyk⁴  Kathrin Gibbert⁴  Jia Liu⁴  Kirsten K. Dietze⁴  Gennadiy Zelinskyy⁴  Ulf Dittmer⁵  C. Preston Neff⁵ 

[1] Department of Immunobiology, Yale School of Medicine, Yale University, New Haven, Connecticut, United States of America;Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China;Institute for Immunology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;University of Colorado, Anschutz Medical Campus, Aurora, Colorado, United States of America

关键词: T cells;    Cytotoxic T cells;    Spleen;    B cells;    Respiratory infections;    Flow cytometry;    Cell staining;    T cell receptors;   

DOI  :  10.1371/journal.ppat.1005224

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY