TY - JOUR
T1 - The requirement of CD8+ T cells to initiate and augment acute cardiac inflammatory response to high blood pressure
AU - Ma, Feifei
AU - Feng, Jin
AU - Zhang, Chao
AU - Li, Yulin
AU - Qi, Guanming
AU - Li, Huihua
AU - Wu, Yuzhang
AU - Fu, Yangxin
AU - Zhao, Yang
AU - Chen, Hairong
AU - Du, Jie
AU - Tang, Hong
PY - 2014/4/1
Y1 - 2014/4/1
N2 - 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-γ that drove IFN-γR+ CD8+ T cell infiltration and activation. Thus, this work identified a TCRindependent innate nature of CD8+ T cells that was critical in initiating the sterile immune response to acute elevation of blood pressure. The Journal of Immunology, 2014, 192: 3365-3373.
AB - 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-γ that drove IFN-γR+ CD8+ T cell infiltration and activation. Thus, this work identified a TCRindependent innate nature of CD8+ T cells that was critical in initiating the sterile immune response to acute elevation of blood pressure. The Journal of Immunology, 2014, 192: 3365-3373.
UR - http://www.scopus.com/inward/record.url?scp=84897548852&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897548852&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1301522
DO - 10.4049/jimmunol.1301522
M3 - Article
C2 - 24600037
AN - SCOPUS:84897548852
SN - 0022-1767
VL - 192
SP - 3365
EP - 3373
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -