title: The requirement of CD8+ T cells to initiate and augment acute cardiac inflammatory response to high blood pressure.
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 TCR-independent innate nature of CD8(+) T cells that was critical in initiating the sterile immune response to acute elevation of blood pressure.
authors.affiliation: Key Laboratory of Remodeling-Related Cardiovascular Diseases, Anzhen Hospital of the Capital Medical University, Beijing, China 100029;
authors.forename: Feifei
authors.initials: F
authors.lastname: Ma
authors.forename: Jin
authors.initials: J
authors.lastname: Feng
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.forename: Guanming
authors.initials: G
authors.lastname: Qi
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
authors.forename: Yangxin
authors.initials: Y
authors.lastname: Fu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hairong
authors.initials: H
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
mesh_terms: D019264:Adoptive Transfer; D000804:Angiotensin II; D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005355:Fibrosis / Q000276:immunology; D005434:Flow Cytometry; D006973:Hypertension / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016827:CD8 Antigens; C431698:CD8alpha antigen; D016207:Cytokines; D018836:Inflammation Mediators; D011948:Receptors, Antigen, T-Cell; D000804:Angiotensin II