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Reduced Neointima Formation After Arterial Injury in CD4−/− Mice Is Mediated by CD8(+)CD28(hi) 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−/−...

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Detalles Bibliográficos
Autores principales: Dimayuga, Paul C., Chyu, Kuang‐Yuh, Lio, Wai Man, Zhao, Xiaoning, Yano, Juliana, Zhou, Jianchang, Honjo, Tomoyuki, Shah, Prediman K., Cercek, Bojan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698777/
https://www.ncbi.nlm.nih.gov/pubmed/23702879
http://dx.doi.org/10.1161/JAHA.113.000155
Descripción
Sumario: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.