Requirements for CD8 T-cell migration into the human arterial wall

Human Pathology
Jan GewaltigBarbara C Biedermann

Abstract

Atherosclerotic lesions develop in the arterial intima. Among the leukocytes that accumulate in advanced atherosclerotic plaques, CD8 T cells play a quantitatively important role. They may be involved in disease progression and plaque destabilization, leading to plaque rupture or erosion. These events finally precipitate cardiovascular events. Therefore, we wished to determine the accessibility of the human arterial wall, particularly the arterial intima, for CD8-positive, cytotoxic T lymphocytes. We quantified the number of CD8-positive T cells in the arterial wall using human arterial tissue microarrays. The conditions for efficient cytotoxic T-lymphocyte migration into the arterial wall were determined in an in vitro tissue invasion assay. The invasion pattern of resting or activated cytotoxic T-lymphocyte clones was morphometrically analyzed by confocal microscopy. CD8 T cells represented up to 50% of the lymphocytes in advanced atherosclerotic lesions. Resting CD8-positive cytotoxic T lymphocytes were able to migrate into the arterial intima when it was affected by advanced lesions but not at the earliest stages of the disease. After T-cell receptor and/or proinflammatory cytokine activation, cytotoxic T lymphocytes migrat...Continue Reading

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