title: Activated T Lymphocytes are Essential Drivers of Pathological Remodeling in Ischemic Heart Failure.
abstract: BACKGROUND
  Inappropriately sustained inflammation is a hallmark of chronic ischemic heart failure (HF); however, the pathophysiological role of T lymphocytes is unclear.
  
  
  RESULTS
  Permanent coronary ligation was performed in adult C57BL/6 mice. When compared with sham-operated mice, mice with HF (8 weeks after ligation) exhibited the following features: (1) significant (P<0.05) expansion of circulating CD3+CD8+cytotoxic and CD3+CD4+helper (Th) T lymphocytes, together with increased Th1, Th2, Th17, and regulatory T-cell (Treg) CD4+subsets; (2) significant expansion of CD8+and CD4+T cells in failing myocardium, with increased Th1, Th2, Th17, and Treg CD4+subsets, marked reduction of the Th1/Th2 ratio, augmentation of the Th17/Treg ratio, and upregulation of Th2 cytokines; and (3) significantly increased Th1, Th2, Th17 cells, and Tregs, in the spleen and mediastinal lymph nodes, with expansion of splenic antigen-experienced effector and memory CD4+T cells. Antibody-mediated CD4+T-cell depletion in HF mice (starting 4 weeks after ligation) reduced cardiac infiltration of CD4+T cells and prevented progressive left ventricular dilatation and hypertrophy, whereas adoptive transfer of splenic CD4+T cells (and, to a lesser extent, cardiac CD3+T cells) from donor mice with HF induced long-term left ventricular dysfunction, fibrosis, and hypertrophy in naive recipient mice.
  
  
  CONCLUSIONS
  CD4+T lymphocytes are globally expanded and activated in chronic ischemic HF, with Th2 (versus Th1) and Th17 (versus Treg) predominance in failing hearts, and with expansion of memory T cells in the spleen. Cardiac and splenic T cells in HF are primed to induce cardiac injury and remodeling, and retain this memory on adoptive transfer.
authors.affiliation: From the Division of Cardiovascular Disease, Comprehensive Cardiovascular Center, University of Alabama at Birmingham (S.S.B., M.A.I., M.G., B.P., T.H., S.D.P.); and Medical Service, Birmingham Veterans Administration Medical Center, AL (S.S.B., S.D.P.).
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Bansal
authors.affiliation: From the Division of Cardiovascular Disease, Comprehensive Cardiovascular Center, University of Alabama at Birmingham (S.S.B., M.A.I., M.G., B.P., T.H., S.D.P.); and Medical Service, Birmingham Veterans Administration Medical Center, AL (S.S.B., S.D.P.).
authors.forename: Mohamed Ameen
authors.initials: MA
authors.lastname: Ismahil
authors.affiliation: From the Division of Cardiovascular Disease, Comprehensive Cardiovascular Center, University of Alabama at Birmingham (S.S.B., M.A.I., M.G., B.P., T.H., S.D.P.); and Medical Service, Birmingham Veterans Administration Medical Center, AL (S.S.B., S.D.P.).
authors.forename: Mehak
authors.initials: M
authors.lastname: Goel
authors.affiliation: From the Division of Cardiovascular Disease, Comprehensive Cardiovascular Center, University of Alabama at Birmingham (S.S.B., M.A.I., M.G., B.P., T.H., S.D.P.); and Medical Service, Birmingham Veterans Administration Medical Center, AL (S.S.B., S.D.P.).
authors.forename: Bindiya
authors.initials: B
authors.lastname: Patel
authors.affiliation: From the Division of Cardiovascular Disease, Comprehensive Cardiovascular Center, University of Alabama at Birmingham (S.S.B., M.A.I., M.G., B.P., T.H., S.D.P.); and Medical Service, Birmingham Veterans Administration Medical Center, AL (S.S.B., S.D.P.).
authors.forename: Tariq
authors.initials: T
authors.lastname: Hamid
authors.affiliation: From the Division of Cardiovascular Disease, Comprehensive Cardiovascular Center, University of Alabama at Birmingham (S.S.B., M.A.I., M.G., B.P., T.H., S.D.P.); and Medical Service, Birmingham Veterans Administration Medical Center, AL (S.S.B., S.D.P.).
authors.forename: Gregg
authors.initials: G
authors.lastname: Rokosh
authors.affiliation: From the Division of Cardiovascular Disease, Comprehensive Cardiovascular Center, University of Alabama at Birmingham (S.S.B., M.A.I., M.G., B.P., T.H., S.D.P.); and Medical Service, Birmingham Veterans Administration Medical Center, AL (S.S.B., S.D.P.). sprabhu@uab.edu.
authors.forename: Sumanth D
authors.initials: SD
authors.lastname: Prabhu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006333:Heart Failure / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D016207:Cytokines
keywords: T lymphocytes; adaptive immunity; adoptive transfer; heart failure; inflammation