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.