title: CD4+ T cells promote the transition from hypertrophy to heart failure during chronic pressure overload.
abstract: BACKGROUND
  The mechanisms by which the heart adapts to chronic pressure overload, producing compensated hypertrophy and eventually heart failure (HF), are still not well defined. We aimed to investigate the involvement of T cells in the progression to HF using a transverse aortic constriction (TAC) model.
  
  
  RESULTS
  Chronic HF was associated with accumulation of T lymphocytes and activated/effector CD4(+) T cells within cardiac tissue. After TAC, enlarged heart mediastinal draining lymph nodes showed a high density of both CD4(+) and CD8(+) T-cell subsets. To investigate the role of T cells in HF, TAC was performed on mice deficient for recombination activating gene 2 expression (RAG2KO) lacking B and T lymphocytes. Compared with wild-type TAC mice, RAG2KO mice did not develop cardiac dilation and showed improved contractile function and blunted adverse remodeling. Reconstitution of the T-cell compartment into RAG2KO mice before TAC enhanced contractile dysfunction, fibrosis, collagen accumulation, and cross-linking. To determine the involvement of a specific T-cell subset, we performed TAC on mice lacking CD4(+) (MHCIIKO) and CD8(+) T-cell subsets (CD8KO). In contrast to CD8KO mice, MHCIIKO mice did not develop ventricular dilation and dysfunction. MHCIIKO mice also displayed very low fibrosis, collagen accumulation, and cross-linking within cardiac tissue. Interestingly, mice with transgenic CD4(+) T-cell receptor specific for ovalbumin failed to develop HF and adverse remodeling.
  
  
  CONCLUSIONS
  These results demonstrate for the first time a crucial role of CD4(+) T cells and specific antigen recognition in the progression from compensated cardiac hypertrophy to HF.
authors.affiliation: From the Institut National de la Santé et de la Recherche Médicale UMR1048 (INSERM), Institute of Cardiovascular and Metabolic Diseases (I2MC), Rangueil, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Toulouse III University, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Department of Cardiology, University Hospital of Rangueil, Toulouse, France (J.P., O.L.); and INSERM-UMS 006-Microsurgery Facility, Toulouse, France (C.D., D.C.).
authors.forename: Fanny
authors.initials: F
authors.lastname: Laroumanie
authors.affiliation: From the Institut National de la Santé et de la Recherche Médicale UMR1048 (INSERM), Institute of Cardiovascular and Metabolic Diseases (I2MC), Rangueil, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Toulouse III University, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Department of Cardiology, University Hospital of Rangueil, Toulouse, France (J.P., O.L.); and INSERM-UMS 006-Microsurgery Facility, Toulouse, France (C.D., D.C.).
authors.forename: Victorine
authors.initials: V
authors.lastname: Douin-Echinard
authors.affiliation: From the Institut National de la Santé et de la Recherche Médicale UMR1048 (INSERM), Institute of Cardiovascular and Metabolic Diseases (I2MC), Rangueil, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Toulouse III University, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Department of Cardiology, University Hospital of Rangueil, Toulouse, France (J.P., O.L.); and INSERM-UMS 006-Microsurgery Facility, Toulouse, France (C.D., D.C.).
authors.forename: Joffrey
authors.initials: J
authors.lastname: Pozzo
authors.affiliation: From the Institut National de la Santé et de la Recherche Médicale UMR1048 (INSERM), Institute of Cardiovascular and Metabolic Diseases (I2MC), Rangueil, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Toulouse III University, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Department of Cardiology, University Hospital of Rangueil, Toulouse, France (J.P., O.L.); and INSERM-UMS 006-Microsurgery Facility, Toulouse, France (C.D., D.C.).
authors.forename: Olivier
authors.initials: O
authors.lastname: Lairez
authors.affiliation: From the Institut National de la Santé et de la Recherche Médicale UMR1048 (INSERM), Institute of Cardiovascular and Metabolic Diseases (I2MC), Rangueil, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Toulouse III University, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Department of Cardiology, University Hospital of Rangueil, Toulouse, France (J.P., O.L.); and INSERM-UMS 006-Microsurgery Facility, Toulouse, France (C.D., D.C.).
authors.forename: Florence
authors.initials: F
authors.lastname: Tortosa
authors.affiliation: From the Institut National de la Santé et de la Recherche Médicale UMR1048 (INSERM), Institute of Cardiovascular and Metabolic Diseases (I2MC), Rangueil, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Toulouse III University, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Department of Cardiology, University Hospital of Rangueil, Toulouse, France (J.P., O.L.); and INSERM-UMS 006-Microsurgery Facility, Toulouse, France (C.D., D.C.).
authors.forename: Claire
authors.initials: C
authors.lastname: Vinel
authors.affiliation: From the Institut National de la Santé et de la Recherche Médicale UMR1048 (INSERM), Institute of Cardiovascular and Metabolic Diseases (I2MC), Rangueil, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Toulouse III University, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Department of Cardiology, University Hospital of Rangueil, Toulouse, France (J.P., O.L.); and INSERM-UMS 006-Microsurgery Facility, Toulouse, France (C.D., D.C.).
authors.forename: Christine
authors.initials: C
authors.lastname: Delage
authors.affiliation: From the Institut National de la Santé et de la Recherche Médicale UMR1048 (INSERM), Institute of Cardiovascular and Metabolic Diseases (I2MC), Rangueil, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Toulouse III University, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Department of Cardiology, University Hospital of Rangueil, Toulouse, France (J.P., O.L.); and INSERM-UMS 006-Microsurgery Facility, Toulouse, France (C.D., D.C.).
authors.forename: Denis
authors.initials: D
authors.lastname: Calise
authors.affiliation: From the Institut National de la Santé et de la Recherche Médicale UMR1048 (INSERM), Institute of Cardiovascular and Metabolic Diseases (I2MC), Rangueil, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Toulouse III University, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Department of Cardiology, University Hospital of Rangueil, Toulouse, France (J.P., O.L.); and INSERM-UMS 006-Microsurgery Facility, Toulouse, France (C.D., D.C.).
authors.forename: Marianne
authors.initials: M
authors.lastname: Dutaur
authors.affiliation: From the Institut National de la Santé et de la Recherche Médicale UMR1048 (INSERM), Institute of Cardiovascular and Metabolic Diseases (I2MC), Rangueil, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Toulouse III University, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Department of Cardiology, University Hospital of Rangueil, Toulouse, France (J.P., O.L.); and INSERM-UMS 006-Microsurgery Facility, Toulouse, France (C.D., D.C.).
authors.forename: Angelo
authors.initials: A
authors.lastname: Parini
authors.affiliation: From the Institut National de la Santé et de la Recherche Médicale UMR1048 (INSERM), Institute of Cardiovascular and Metabolic Diseases (I2MC), Rangueil, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Toulouse III University, Toulouse, France (F.L., V.D.-E., C.V., F.T., M.D., A.P., N.P.); Department of Cardiology, University Hospital of Rangueil, Toulouse, France (J.P., O.L.); and INSERM-UMS 006-Microsurgery Facility, Toulouse, France (C.D., D.C.). nathalie.pizzinat@inserm.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pizzinat
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D006332:Cardiomegaly / Q000276:immunology / Q000473:pathology*; D018450:Disease Progression; D006333:Heart Failure / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic
keywords: heart failure; lymphocytes; ventricular remodeling