PD-1 Dynamically Regulates Inflammation and Development of Brain-Resident Memory CD8 T Cells During Persistent Viral Encephalitis

In this study, we show that PD-1 acts to inhibit the effector functions of virus-specific CD8 bTRM during MuPyV encephalitis. NanoString inflammatory gene expression analysis of brains of wild type (WT) and PD-L1−/− mice infected with MuPyV revealed that PD-1 signaling controls the inflammatory response during acute infection. In striking contrast, the absence of PD-1 signaling during persistent infection resulted in lower neuroinflammation than in WT mice. PD-1 was further found to affect the differentiation of virus-specific CD8 bTRM. Together, these findings reveal a complex, dynamic impact of PD-1 on neuroinflammation and CD8 bTRM formation and activity during persistent viral encephalitis. Materials and Methods Mice and Virus Inoculation C57BL/6NCr (WT) female mice purchased from the Frederick Cancer Research and Development Center of the National Cancer Institute (Frederick, MD) and B7-H1−/− (PD-L1−/−) mice [generously provided by C.C. Bergmann (Lerner Research Institute, Cleveland, OH) with approval of L. Chen (Yale School of Medicine, New Haven, CT)] were housed in accordance with the guidelines of the Institutional Animal Care and Use Committees and the Department of Comparative Medicine at the Pennsylvania State University College of Medicine. The Pennsylvania State University College of Medicine Animal Resource Program is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care Inter...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research