Mechanisms of cell-mediated myotoxicity. Morphological observations in muscle grafts and in muscle exposed to sensitized spleen cells in vivo.

Fragments of rectus abdominis muscle or diaphragm from AKR or Prince Henry mice were transplanted beneath the skin of the anterior abdominal wall of BALB/C mice and were examined by light and electron microscopy 1-23 days after transplantation. Observations were made on the mode of entry of lymphoid cells into grafts, the nature of the inflammatory cells present in grafts and the interactions between mononuclear cells and regenerating muscle fibres during the rejection phase 7-14 days after transplantation. Lymphoid cells were found to migrate through the endothelium of venules and to enter the space between the basement lamina and the plasma membrane of muscle fibres to make contacts of varying degrees of complexity with the muscle cell membrane. Evidence of penetration of lymphoid cells into muscle fibres (emperipolesis) was found and was usually associated with signs of damage to the muscle fibre. Interactions between mononuclear cells and mature muscle fibres were studied after inoculation of sensitized spleen cells into the musculature of the tongue in mice. Both lymphoid cells and mononuclear phagocytes were found to invade muscle fibres by penetrating the basement lamina. The muscle cell membrane was usually broken down in zones of invasion by mononuclear cells but generally remained intact at sites of invasion by lymphoid cells.