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(Circulation. 1998;97:637-639.)
© 1998 American Heart Association, Inc.

Brief Rapid Communications

Expression of Costimulatory Molecules B7–1, B7–2, and CD40 in the Heart of Patients With Acute Myocarditis and Dilated Cardiomyopathy

Yoshinori Seko, MD; Naoyuki Takahashi, MD; Shigeru Ishiyama, MD; Toshiro Nishikawa, PhD; Takeshi Kasajima, PhD; Michiaki Hiroe, MD; Shin Suzuki, MD; Sugao Ishiwata, MD; Sachio Kawai, MD; Miyuki Azuma, PhD; Hideo Yagita, PhD; Ko Okumura, PhD; ; Yoshio Yazaki, MD

From the Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo (Y.S., N.T., Y.Y.); Department of Immunology (Y.S., H.Y., K.O.), Division of Cardiology, and Department of Internal Medicine (S.K.), School of Medicine, Juntendo University, Tokyo; Cardiovascular Center, Department of Cardiology, Toranomon Hospital, Tokyo (S. Ishiwata); Department of Immunology, National Children's Medical Research Center, Tokyo (M.A.); Institute for Adult Diseases, Asahi Life Foundation, Tokyo (Y.S.); Second Department of Pathology, Tokyo Women's Medical College (S. Ishiyama, T.N., T.K.); Second Department of Internal Medicine, School of Medicine, Tokyo Medical and Dental University (S. Ishiyama, M.H.); and Department of Cardiology, Sakakibara Heart Institute, Tokyo (S.S.), Japan.

Correspondence to Yoshinori Seko, MD, Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.

Background—In patients with acute myocarditis and dilated cardiomyopathy (DCM), we previously reported that antigen-specific T cells infiltrate the heart and play an important role in the myocardial damage involved. For antigen-specific T-cell activation to occur, it is necessary for T cells to receive a costimulatory signal provided by costimulatory molecules expressed on antigen-presenting cells (APCs) as well as the main signal provided by binding of T-cell receptors to the antigen.

Methods and Results—To investigate the roles of the costimulatory molecules B7–1, B7–2, and CD40 in the development of acute myocarditis and DCM, we analyzed the expression of these antigens in the myocardial tissues of patients with acute myocarditis and DCM. We also examined the expression of a cytolytic factor, perforin, in the infiltrating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, because both killer lymphocytes are thought to damage B7–1–expressing APCs. We found that B7–1, B7–2, and CD40 were moderately to strongly expressed in the cardiac myocytes of patients with acute myocarditis. Weak to moderate expression of these antigens was also found in the cardiac myocytes of patients with DCM. There was infiltration of perforin-expressing CTLs and NK cells in the myocardial tissues of patients with acute myocarditis and DCM.

Conclusions—Our findings strongly suggest that expression of B7–1, B7–2, and CD40 antigens on cardiac myocytes may make them APCs for CTLs and NK cells and that they may play an important role in the direct myocardial damage by these killer cells in acute myocarditis and DCM.

Key Words: myocarditis • cardiomyopathy • immunology • immunohistochemistry

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