Condotta, Stephanie A.Downey, JeffreyPardy, Ryan D.Valbon, Stefanie F.Tarrab, EstherLamarre, AlainDivangahi, MaziarRicher, Martin J.2022-01-282022-01-282020-04Condotta, S. A., Downey, J., Pardy, R. D., Valbon, S. F., Tarrab, E., Lamarre, A., Divangahi, M., & Richer, M. J. (2020). Cyclophilin D Regulates Antiviral CD8+ T Cell Survival in a Cell-Extrinsic Manner. ImmunoHorizons, 4(4), 217–230. https://doi.org/10.4049/immunohorizons.2000016https://hdl.handle.net/1805/27624CD8+ T cell–mediated immunity is critical for host defense against viruses and requires mitochondria-mediated type I IFN (IFN-I) signaling for optimal protection. Cyclophilin D (CypD) is a mitochondrial matrix protein that modulates the mitochondrial permeability transition pore, but its role in IFN-I signaling and CD8+ T cell responses to viral infection has not been previously explored. In this study, we demonstrate that CypD plays a critical extrinsic role in the survival of Ag-specific CD8+ T cell following acute viral infection with lymphocytic choriomeningitis virus in mice. CypD deficiency resulted in reduced IFN-I and increased CD8+ T cell death, resulting in a reduced antiviral CD8+ T cell response. In addition, CypD deficiency was associated with an increase in pathogen burden at an early time-point following infection. Furthermore, our data demonstrate that transfer of wild-type macrophages (expressing CypD) to CypD-deficient mice can partially restore CD8+ T cell responses. These results establish that CypD plays an extrinsic role in regulating optimal effector CD8+ T cell responses to viral infection. Furthermore, this suggests that, under certain circumstances, inhibition of CypD function may have a detrimental impact on the host’s ability to respond to viral infection.enAttribution 4.0 InternationalCyclophilin DCD8+ T cell responsesviral infectionArticle