101. Nasal vaccination with troponin reduces troponin specific T-cell responses and improves heart function in myocardial ischemia–reperfusion injury
- Author
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Alok S. Pachori, Sanja Petrovic-Stojkovic, Howard L. Weiner, Dorit Farfara, Victor J. Dzau, Dan Frenkel, Adi Dembinsky-Vaknin, and Lunan Zhang
- Subjects
CD4-Positive T-Lymphocytes ,Cellular immunity ,medicine.medical_specialty ,medicine.medical_treatment ,T cell ,Immunology ,Ischemia ,Inflammation ,Myocardial Reperfusion Injury ,Interferon-gamma ,Mice ,Internal medicine ,medicine ,Immunology and Allergy ,Animals ,Protein Isoforms ,Administration, Intranasal ,Mice, Knockout ,biology ,business.industry ,Myocardium ,Vaccination ,General Medicine ,medicine.disease ,Troponin ,Adoptive Transfer ,Interleukin-10 ,Mice, Inbred C57BL ,Disease Models, Animal ,Cytokine ,medicine.anatomical_structure ,biology.protein ,Cardiology ,Nasal administration ,Female ,medicine.symptom ,business ,Reperfusion injury ,Original Research Papers - Abstract
Myocardial ischemia with subsequent reperfusion (MI/R) can lead to significant myocardial damage. Ischemia initiates inflammation at the blood-microvascular endothelial cell interface and contributes significantly to both acute injury and repair of the damaged tissue. We have found that MI/R injury in mice is associated with a cellular immune response to troponin. Myocardial cells exclusively synthesize troponin and release the troponin into the bloodstream following injury. Mucosally administered proteins induce T cells that secrete anti-inflammatory cytokines such as IL-10 and transforming growth factor beta at the anatomical site where the protein localizes. We found that nasal administration of the three subunits of troponin (C, I and T isoforms), given prior to or 1 h following MI/R, decreased infarct size by 40% measured 24 h later. At 1.5 months following MI/R, there was a 50% reduction in infarct size and improvement in cardiac function as measured by echocardiography. Protection was associated with a reduction of cellular immunity to troponin. Immunohistochemistry demonstrated increased IL-10 and reduced IFN-gamma in the area surrounding the ischemic infarct following nasal troponin. Adoptive transfer of CD4+ T cells to mice from nasally troponin-treated mice 1 h after the MI/R decreased infarct size by 72%, whereas CD4+ T cells from IL-10-/- mice or nasally BSA-treated mice had no effect. Our results demonstrate that IL-10-secreting CD4+ T cells induced by nasal troponin reduce injury following MI/R. Modulation of cardiac inflammation by nasal troponin provides a novel treatment to decrease myocardial damage and enhance recovery after myocardial ischemia.
- Published
- 2009