PT - JOURNAL ARTICLE AU - Condotta, Stephanie A. AU - Downey, Jeffrey AU - Pardy, Ryan D. AU - Valbon, Stefanie F. AU - Tarrab, Esther AU - Lamarre, Alain AU - Divangahi, Maziar AU - Richer, Martin J. TI - Cyclophilin D Regulates Antiviral CD8<sup>+</sup> T Cell Survival in a Cell-Extrinsic Manner AID - 10.4049/immunohorizons.2000016 DP - 2020 Apr 01 TA - ImmunoHorizons PG - 217--230 VI - 4 IP - 4 4099 - http://www.immunohorizons.org/content/4/4/217.short 4100 - http://www.immunohorizons.org/content/4/4/217.full AB - CD8+ 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.