Reduced Neointima Formation After Arterial Injury in CD 4−/− Mice Is Mediated by CD 8 + CD 28 hi T Cells

Background CD 8 + T ‐cell activation, characterized by increased CD 28 expression, reduces neointima formation after arterial injury in mice. The CD 8 + CD 28 hi phenotype is associated with increased effector function. In this study, we used a mouse model that has CD 8 + but no CD 4 + T cells ( CD 4−/−) to assess the role of CD 8 + T cells and test the function of CD 8 + CD 28 hi T cells in modulating neointima formation after arterial injury. Methods and Results Neointima formation after pericarotid arterial cuff injury was significantly less in CD 4−/− mice compared with wild‐type ( WT ) mice. Negligible baseline lytic activity by splenic CD 8 + T cells from uninjured WT mice against target syngeneic smooth muscle cells was significantly increased 7 days after injury. Interestingly, CD 8 + T cells from uninjured CD 4−/− mice had significant lytic activity at baseline that remained elevated 7 days after injury. CD 8 + T ‐cell lytic activity was significantly reduced by depletion of CD 28 hi cells. CD 8 + CD 28 hi T cells adoptively transferred into recipient Rag‐1−/− mice significantly reduced neointima formation compared with CD 8 + CD 28 + T ‐cell recipient mice. Conclusions CD 8 + T cells reduced neointima formation after arterial injury, attributed in part to increased function of the CD 8 + CD 28 hi phenotype.