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(Circulation. 1995;92:2876-2885.)
© 1995 American Heart Association, Inc.

Articles

Phenotypic Patterns of Mononuclear Cells in Dilated Cardiomyopathy

Christoph Holzinger, MD; Andrea Schöllhammer, MD; Martin Imhof, MD; Christian Reinwald, MD; Gero Kramer, MD; Andreas Zuckermann, MD; Ernst Wolner, MD; Georg Steiner, Director

From the Second Department of Surgery (C.H., M.I., A.Z., E.W.) and Department of Urology (A.S., C.R., G.K., G.S.), University of Vienna, Austria.

Correspondence to Dr Christoph Holzinger, Allgemeines Krankenhaus Wien, Abteilung Herz- und Thoraxchirurgie, Währinger Gürtel 18-20, A-1090 Vienna, Austria.

Background Immunological factors in the pathogenesis of idiopathic dilated cardiomyopathy (IDC) were suggested previously on the basis of the demonstration of mononuclear cell infiltrates and autoantibodies against the myocardium. The present study investigated whether tissue leukocyte subpopulations isolated from hearts with IDC (n=6) differ in phenotype from those of tissues without IDC (n=7).

Methods and Results Leukocytes were quantified as reactive cells per square millimeter in perivascular, interstitial, and parenchymal tissue sections. Freshly isolated heart-tissue T cells and peripheral-blood T cells from the same patients were analyzed by triple staining and flow cytometry to identify T-cell subpopulations as well as their states of differentiation (expression of CD45RA and Leu-8 versus CD45RO) and activation (IL-2R, IL-7R, very late antigen–1, HLA-DR). All types of infiltrating cells (T cells, B cells, macrophages, granulocytes) are increased in hearts with IDC compared with normal hearts, but only CD8⁺ T cells and macrophages are increased relative to the other leukocyte subpopulations. CD45RO⁺/CD45RA^-/Leu-8^- cells constitute the majority of heart-tissue T cells in both normal hearts and hearts with IDC. Strikingly, hearts with IDC are infiltrated by eightfold greater numbers of perivascularly located IL-2R⁺– (26% of all T cells) and CD45RO⁺–activated memory T cells; moreover, in contrast to normal heart, 40% of both CD4⁺ and CD8⁺ heart-tissue T cells express activation markers.

Conclusions Both normal hearts and hearts with IDC are populated by leukocytes. The quantitative increase in IDC, associated with a dramatically altered activation status of heart-tissue T cells, suggests a direct role of infiltrating leukocytes in the pathogenesis of IDC.

Key Words: cardiomyopathy • lymphocytes • genes • cells

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