CD8+ T lymphocytes mediate destruction of the vascular media in a model of chronic rejection.

Allograft arteriosclerosis is an important characteristic of chronic graft rejection. In allograft arteriosclerosis there is a striking loss of medial smooth muscle cells (SMCs) before the development of a concentric intimal proliferative response. In this study we evaluated the role of CD8+ T lymphocytes in this medial SMC loss. Brown Norway aortic segments were transplanted into Lewis animals for 60 days (long allo-exposure) or 20 days (short allo-exposure). After 20 days allogeneic exposure aortic segments were transplanted back into syngeneic (Brown Norway) animals for 40 days. Experimental animals were treated with mAb to CD8. Apoptosis was measured by terminal dUTP nick-end labeling at 20 days and morphometry analyzed at 60 days to evaluate medial and intimal changes. Anti-CD8 treatment significantly lowered CD8+ T cell counts in peripheral blood, reduced medial SMC apoptosis at 20 days, and increased medial SMC counts at 60 days. Both short- and long-allogeneic exposure groups confirmed these findings and demonstrated that medial SMC loss is proportional to the length of allogeneic exposure. Antibody depletion of CD8+ T cells results in reduced medial SMC apoptosis and better medial SMC preservation. This supports the hypothesis that medial SMC loss occurs by apoptotic death and is driven by CD8+ T lymphocytes.