Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice

• DOI: 10.1084/jem.20121015
• Publication Date: 2012-12-11T03:58:10Z
• Authors: Helge Frebel; Veronika Nindl; Reto A. Schuepbach; Thomas Braunschwe...; Kirsten Richter; Johannes Vogel; Carsten A. Wagner; Dominique Loffing...; Michael Kurrer; Burkhard Ludewig; Annette Oxenius
• Keywords: Pathogenesis

The inhibitory programmed death 1 (PD-1)–programmed ligand (PD-L1) pathway contributes to the functional down-regulation of T cell responses during persistent systemic and local virus infections. blockade PD-1–PD-L1–mediated inhibition is considered as a therapeutic approach reinvigorate antiviral responses. Yet previous studies reported that PD-L1–deficient mice develop fatal pathology early lymphocytic choriomeningitis (LCMV) infection, suggesting host protective role down-regulation. As exact mechanisms development remained unclear, we set out delineate in detail underlying pathogenesis. Mice deficient PD-1–PD-L1 signaling or lacking PD-1 CD8 cells succumbed cell–mediated immunopathology after LCMV infection. In absence regulation via PD-1, killed infected vascular endothelial perforin-mediated cytolysis, thereby severely compromising integrity. This resulted leakage consequential collapse circulatory system. Our results indicate protects system from severe damage highlighting pivotal physiological potential immunopathological side effects when interfering with