Abstract 516: CD8+ T Cells Inhibit Intimal Thickening In Mice Independent Of The MHC-I Molecule H-2Db
Background: We have reported that intimal thickening after arterial cuff injury is preferentially inhibited by CD8+ T cells. However, the activation pathway that drives this response remained unknown. We characterized CD8+ T cell activation and determined if TCR-MHC-I pathway was involved in CD8+ T cell response to arterial injury.
Methods and Results: Splenic T cells from CD4KO mice were adoptively transferred to Rag-1KO mice (both in C57Bl/6 background) which were subjected to arterial cuff injury 48 hours later. Transferred cells were characterized by staining for surface activation markers before transfer, 48 hour post-transfer before injury, and 21 days after injury. MHC-I signaling was blocked in recipient Rag-1KO mice using a monoclonal anti-H-2Db antibody (mAb, 0.2mg/mouse) on the day of cell transfer, at injury, and twice weekly until day 14. Intimal area was measured 21 days after injury. CD8 T cells were detected in PBMC of recipient Rag-1KO mice 48 hours post-transfer and persisted until 21 days after injury. Splenic CD8 T cells from recipient Rag-1KO mice 48 hours post-cell transfer showed decreased CD8+CD62Lhi T cells, which persisted until 21 days after injury; indicating activation of CD8 T-cells. CD8+CD44hi T cells were unchanged 48 hours post-transfer but were increased 21 days after injury. Twenty-one days after injury IFN-γ and CD28 expression increased 3- and 6-fold, respectively. Blocking with H-2Db antibody in vivo resulted in 50% decrease in activated CD8-T cells in the recipients but intimal thickening was not affected.
Conclusion: Arterial injury results in activation of splenic CD8+ T cells, marked by decreased CD62L and increased CD44 surface expression, and increased mRNA expression of IFN-γ and CD28. However, the activation is only partially mediated by, and the effect on intimal thickening is independent of, the MHC-I molecule H-2Db.