[Cytotoxic factor in vascular injury]

Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of vascular injury in Takayasu's arteritis. Both cytotoxic T lymphocytes (CTLs) and natural killer (NK)cells, playing a major part in cell-mediated cytotoxicity, are thought to kill virus-infected cells or tumor cells with the effector molecules contained in their cytoplasmic granules, one of which is named pore-forming protein or perforin. Perforin is expected to play a central role in the granule exocytosis model of lymphocyte-mediated cytolysis, exhibited by CTLs and NK cells as well as gamma delta T lymphocytes. We found that perforin was expressed in these killer lymphocytes infiltrated in the aortic tissue of patients with Takayasu's arteritis. Immunoelectron microscopic study demonstrated that the infiltrating cells directly injured vascular cells by releasing perforin molecules, indicating the critical role of perforin in the vascular injury involved in Takayasu's arteritis.