Lysis of myotubes by alloreactive cytotoxic T cells and natural killer cells. Relevance to myoblast transplantation

Abstract

The aim of this study was to investigate the susceptibility of human myotubes to lysis by the two major types of cytotoxic effector cells, CD3+CD8+ cytotoxic T cells (CTL) and CD16+CD56+ natural killer (NK) cells. The myoblasts preparations used as target cells were greater than 90% pure as assessed by immunostaining with the Leu19 monoclonal antibody (MAb) that cross-reacts with the neural cell adhesion molecule N-CAM. Allospecific CTL lines were generated from mixed lymphocyte cultures, and freshly isolated allogeneic and autologous peripheral blood cells were used as a source of NK cells. The cytotoxicity was observed under phase optics and by immunoelectron microscopy, and was quantitated with a chromium release assay. Myotubes were efficiently killed by allospecific CTL and by autologous and allogeneic NK cells. The killing by CTL was inhibited with an anti-class I HLA MAb, and the killing by NK cells was inhibited by depleting peripheral blood cells of CD16+ cells with anti-CD16 MAb and complement. The results have important implications for myoblast transplantation, an experimental therapy of muscular dystrophy.