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CD4+ T cells Regulate Cardiac Ischemia/Reperfusion Injury
Author(s) -
Zuidema Mozow Yusof,
Li Jun,
Lee Sewon,
Meininger Gerald A,
Hill Michael A,
Dellsperger Kevin C,
Zhang Cuihua
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1136.13
Subject(s) - inflammation , cardiac function curve , immune system , medicine , innate immune system , monocyte , cytokine , reperfusion injury , myocardial infarction , acquired immune system , immunology , endocrinology , ischemia , heart failure
The mechanisms of healing following myocardial infarction are multifaceted. We tested the hypothesis that chronic, post‐ischemic, cardiac inflammation is regulated by CD4+ T cells through cytokine release and metabolism, and this leads to impaired cardiac function. For these studies, a mouse model of myocardial I/R (30 minutes/24 hours) was employed using wild type (WT) C57Bl/6J mice and CD4+ −/− mice. Based on several hemodynamic measures (EF, SW, dP/dtmax), the cardiac function of CD4+ −/− mice was impaired. Significant induction of monocyte chemotactic protein‐1 (1.9x; MCP‐1) and interferon gamma (3.4x; IFNγ) protein expression occurred following I/R in WT but was absent in CD4+ −/− (n=4; p<0.05). These observations suggested that CD4+ T cells play a pivotal role in the recruitment of innate immune responses following I/R. CD4+ −/− mice had increased cardiac TNFα (3x), ADAM10 (3x), ADAM17 (1.5x), and TLR‐2 (2.3x) mRNA expression relative to WT (n=5; p<0.05). Collectively, these results suggest that CD4+ T cells mediate cardiac dysfunction via TNFα metabolism and inflammatory cascades linked to MCP‐1, IFNγ, and TLR‐2. We propose that CD4+ T cells may bridge the innate immune response to the adaptive immune response in cardiac I/R. This may provide novel mechanistic strategies to target CD4+ T cells and treat chronic reperfusion injury syndromes. Supported by HL077566, HL085119, AHA SDG and AHA 10POST3870022.