Division of Cardiology, Oppenheimer Atherosclerosis Research Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
PLoS One. 2011;6(5):e20214. doi: 10.1371/journal.pone.0020214. Epub 2011 May 24.
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.
T 细胞调节动脉损伤后的新生内膜形成，但对动脉损伤后被激活的特定 T 细胞群体仍不清楚。本研究的目的是鉴定在小鼠动脉损伤后被激活并调节新生内膜增厚的 T 细胞群体。在野生型 C57Bl6 小鼠中，动脉损伤导致 T 细胞激活，表现为淋巴结和脾脏中 CD4(+)CD44(hi)和 CD8(+)CD44(hi)T 细胞增加。脾 CD8(+)CD25(+)T 细胞和 CD8(+)CD28(+)T 细胞也明显增加，而 CD4(+)CD25(+)和 CD4(+)CD28(+)T 细胞则没有增加。分别从 CD8-/-或 CD4-/-供体小鼠中过继转移 CD4(+)或 CD8(+)T 细胞到免疫缺陷 Rag-1-/-小鼠中，以确定抑制动脉损伤后新生内膜形成的 T 细胞亚群。与未进行细胞转移的 Rag-1-/-小鼠相比，接受 CD8(+)T 细胞转移的 Rag-1-/-小鼠的新生内膜形成明显减少。CD4(+)T 细胞转移不能减少新生内膜形成。来自 CD4-/-小鼠的 CD8(+)T 细胞在体外对同种平滑肌细胞具有细胞毒性活性。研究表明，尽管 CD8(+)T 细胞和 CD4(+)T 细胞在动脉损伤后均被激活，但过继性细胞转移鉴定出 CD8(+)T 细胞是抑制新生内膜形成的特定和选择性细胞类型。
