Reduced Neointima Formation After Arterial Injury in CD4−/− Mice Is Mediated by CD8+CD28hi T Cells

BACKGROUND CD8(+) T-cell activation, characterized by increased CD28 expression, reduces neointima formation after arterial injury in mice. The CD8(+)CD28(hi) phenotype is associated with increased effector function. In this study, we used a mouse model that has CD8(+) but no CD4(+) T cells (CD4-/-) to assess the role of CD8(+) T cells and test the function of CD8(+)CD28(hi) T cells in modulating neointima formation after arterial injury. METHODS AND RESULTS Neointima formation after pericarotid arterial cuff injury was significantly less in CD4-/- mice compared with wild-type (WT) mice. Negligible baseline lytic activity by splenic CD8(+) T cells from uninjured WT mice against target syngeneic smooth muscle cells was significantly increased 7 days after injury. Interestingly, CD8(+) T cells from uninjured CD4-/- mice had significant lytic activity at baseline that remained elevated 7 days after injury. CD8(+) T-cell lytic activity was significantly reduced by depletion of CD28(hi) cells. CD8(+)CD28(hi) T cells adoptively transferred into recipient Rag-1-/- mice significantly reduced neointima formation compared with CD8(+)CD28(+) T-cell recipient mice. CONCLUSIONS CD8(+) T cells reduced neointima formation after arterial injury, attributed in part to increased function of the CD8(+)CD28(hi) phenotype.