The requirement of CD8+ T cells to initiate and augment acute cardiac inflammatory response to high blood pressure

Feifei Ma, Jin Feng, Chao Zhang, Yulin Li, Guanming Qi, Huihua Li, Yuzhang Wu, Yangxin Fu, Yang Zhao, Hairong Chen, Jie Du, Hong Tang

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3365-3373
Number of pages9
JournalJournal of Immunology
Volume192
Issue number7
DOIs
StatePublished - Apr 1 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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