The Role of Heart Infiltrating Cells in Myocyte Injury

Abstract

There remains considerable uncertainity regarding the mechanisms of myocyte injury that is caused during myocarditis, or cardiac allograft rejection. Many investigators have proposed that immune mediated cardiac injury is due to an effect of CD8+ cytotoxic T lymphocytes (CTL). CTL may directly injure cardiac myocytes in an allospecific manner, by reacting with major histocompatibility complex (MHC) class 1 antigens expressed on the surface of the myocyte in the case of transplant rejection, or by reacting against viral antigens expressed on the surface of the myocyte in the case of myocarditis (for review see Barry 1994). Indeed there is considerable evidence that CD8+ CTLs can cause injury or lysis of cardiac myocytes in a variety of experimental situations. The work of Felzen et al. (1994) has demonstrated that Con A-activated CTL can induce lysis of cardiac myocytes. Hassin et al. (1987) showed that lymphocytes isolated from the spleen of Mingo virus infected rats can lyse Mingo virus infected cultured cardiac myocytes, and Huber et al. (1984) have demonstrated CTL-mediated lysis of Coxsackie virus infected myocytes by sensitized CTL. Work from our group (Woodley et al. 1991; Ensley et al. 1994) has demonstrated that CD8+ CTL obtained from a mixed lymphocyte reaction (MLR) in a murine heterotopic transplant model can induce contractile abnormalities and lysis of cultured fetal murine cardiac ventricular myocytes in an allospecific manner.