| First Author | Ma F | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 7 | Pages | 3365-73 |
| PubMed ID | 24600037 | Mgi Jnum | J:210252 |
| Mgi Id | MGI:5569866 | Doi | 10.4049/jimmunol.1301522 |
| Citation | Ma F, et al. (2014) The requirement of CD8+ T cells to initiate and augment acute cardiac inflammatory response to high blood pressure. J Immunol 192(7):3365-73 |
| abstractText | Macrophage infiltration and activation in myocardium are hallmarks of acute cardiac inflammatory response to high blood pressure. However, the underlying mechanisms remain elusive. In this article, we report that CD8(+) T cells are required for cardiac recruitment and activation of macrophages. First, mice with CD8 gene-targeted (CD8 knockout) or CD8(+) T cells depleted by Ab showed significantly reduced cardiac inflammatory response to the elevation of blood pressure after angiotensin II (Ang II) infusion, whereas CD8 knockout mice reconstituted with CD8(+) T cells restored the sensitivity to Ang II. More importantly, CD8(+) T cells were required for macrophage infiltration in myocardium and subsequent activation to express proinflammatory cytokines and chemokines. Furthermore, macrophage activation required direct contact with activated CD8(+) T cells, but with TCR dispensable. TCR-independent activation of macrophages was further confirmed in MHC class I-restricted OVA-specific TCR transgenic mice, which showed a CD8(+) T cell activation and cardiac proinflammatory response to Ang II similar to that of wild-type mice. Finally, only myocardium-infiltrated, but not peripheral, CD8(+) T cells were specifically activated by Ang II, possibly by the cardiac IFN-gamma that drove IFN-gammaR(+) CD8(+) T cell infiltration and activation. Thus, this work identified a TCR-independent innate nature of CD8(+) T cells that was critical in initiating the sterile immune response to acute elevation of blood pressure. |
