Enhanced Neointima Formation Following Arterial Injury in Immune Deficient Rag-1−/− Mice Is Attenuated by Adoptive Transfer of CD8 ⁺ T cells

Abstract

T cells modulate neointima formation after arterial injury but the specific T cell population that is activated in response to arterial injury remains unknown. The objective of the study was to identify the T cell populations that are activated and modulate neointimal thickening after arterial injury in mice. Arterial injury in wild type C57Bl6 mice resulted in T cell activation characterized by increased CD4 ⁺CD44 ^hi and CD8 ⁺CD44 ^hi T cells in the lymph nodes and spleens. Splenic CD8 ⁺CD25 ⁺ T cells and CD8 ⁺CD28 ⁺ T cells, but not CD4 ⁺CD25 ⁺ and CD4 ⁺CD28 ⁺ T cells, were also significantly increased. Adoptive cell transfer of CD4 ⁺ or CD8 ⁺ T cells from donor CD8−/− or CD4−/− mice, respectively, to immune-deficient Rag-1−/− mice was performed to determine the T cell subtype that inhibits neointima formation after arterial injury. Rag-1−/− mice that received CD8 ⁺ T cells had significantly reduced neointima formation compared with Rag-1−/− mice without cell transfer. CD4 ⁺ T cell transfer did not reduce neointima formation. CD8 ⁺ T cells from CD4−/− mice had cytotoxic activity against syngeneic smooth muscle cells in vitro. The study shows that although both CD8 ⁺ T cells and CD4 ⁺ T cells are activated in response to arterial injury, adoptive cell transfer identifies CD8 ⁺ T cells as the specific and selective cell type involved in inhibiting neointima formation.