title: T cell costimulation blockade blunts pressure overload-induced heart failure.
abstract: Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant functions of individual cytokines. Searching for better cardiac inflammation targets, here we link T cells with HF development in a mouse model of pathological cardiac hypertrophy and in human HF patients. T cell costimulation blockade, through FDA-approved rheumatoid arthritis drug abatacept, leads to highly significant delay in progression and decreased severity of cardiac dysfunction in the mouse HF model. The therapeutic effect occurs via inhibition of activation and cardiac infiltration of T cells and macrophages, leading to reduced cardiomyocyte death. Abatacept treatment also induces production of anti-inflammatory cytokine interleukin-10 (IL-10). IL-10-deficient mice are refractive to treatment, while protection could be rescued by transfer of IL-10-sufficient B cells. These results suggest that T cell costimulation blockade might be therapeutically exploited to treat HF.
authors.affiliation: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.|Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, Rozzano, 20089 Milan, Italy.
authors.forename: Marinos
authors.identifier: 0000-0001-9318-3368
authors.initials: M
authors.lastname: Kallikourdis
authors.affiliation: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Martini
authors.affiliation: Department of Cardiovascular Medicine, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.|Institute of Genetic and Biomedical Research (IRGB)-UOS of Milan, National Research Council of Italy, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
authors.forename: Pierluigi
authors.identifier: 0000-0003-0812-7770
authors.initials: P
authors.lastname: Carullo
authors.affiliation: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sardi
authors.affiliation: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Roselli
authors.affiliation: Department of Cardiovascular Medicine, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
authors.forename: Carolina M
authors.identifier: 0000-0002-9895-5635
authors.initials: CM
authors.lastname: Greco
authors.affiliation: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Vignali
authors.affiliation: Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Via Celoria 10, 20133 Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Riva
authors.affiliation: KG Jebsen Centre of Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Postboks 8905, 7491 Trondheim, Norway.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Ormbostad Berre
authors.affiliation: KG Jebsen Centre of Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Postboks 8905, 7491 Trondheim, Norway.|Norwegian Health Association, Oscars gate 36A, 0258 Oslo, Norway.
authors.forename: Tomas O
authors.initials: TO
authors.lastname: Stølen
authors.affiliation: Cardiac Surgery, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fumero
authors.affiliation: Department of Cardiac Surgery, University of Verona, 37129 Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Faggian
authors.affiliation: Department of Cardiovascular Medicine, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.|Institute of Genetic and Biomedical Research (IRGB)-UOS of Milan, National Research Council of Italy, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Di Pasquale
authors.affiliation: Department of Cardiovascular Medicine, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.|Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Elia
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Trentacoste 2, 20133 Milan, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rumio
authors.affiliation: Institute of Genetic and Biomedical Research (IRGB)-UOS of Milan, National Research Council of Italy, Via Manzoni 56, Rozzano, 20089 Milan, Italy.|Laboratory of Signal Transduction in Cardiac Pathologies, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
authors.forename: Daniele
authors.identifier: 0000-0001-7041-6114
authors.initials: D
authors.lastname: Catalucci
authors.affiliation: Department of Cardiovascular Medicine, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.|Institute of Genetic and Biomedical Research (IRGB)-UOS of Milan, National Research Council of Italy, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Papait
authors.affiliation: Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, Rozzano, 20089 Milan, Italy.|Department of Cardiovascular Medicine, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
authors.forename: Gianluigi
authors.identifier: 0000-0003-0481-6843
authors.initials: G
authors.lastname: Condorelli
mesh_terms: D000069594:Abatacept / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D002478:Cells, Cultured; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011312:Pressure; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D016753:Interleukin-10; D000069594:Abatacept