HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I (HTLV-1)-SPECIFIC CD8(-I-ASSOCIATED NEUROLOGIC DISEASE SECRETE PROINFLAMMATORY CYTOKINES, CHEMOKINES, AND MATRIX METALLOPROTEINASE() CTL CLONES FROM PATIENTS WITH HTLV)

Human T cell leukemia virus type I (HTLV-I)-associated myelopathy/trop ical spastic paraparesis (HAM/TSP) is a chronic, progressive neurologi c disease characterized by marked degeneration of the spinal cord and the presence of infiltrating CD8(+) T cells and macrophages, HAM/TSP p atients have very high frequencies of HTLV-I-specific CD8(+) CTL in pe ripheral blood and in cerebrospinal fluid, In this study, we show that HAM/TSP patients also have elevated levels of peripheral blood CD8(+) T cells that produce intracellular IFN-gamma. To address the potentia l role of soluble mediators secreted by CD8(+) T cells in the pathogen esis of HAM/TSP, we have analyzed the capacity of a panel of nine HTLV -l-specific CD8(+) CTL clones derived from three HAM/TSP patients to s ecrete cytokines, chemokines, and matrix metalloproteinases. The resul ts demonstrate that the majority of these CTL clones secrete IFN-gamma , TNF-alpha, macrophage-inflammatory protein-1 alpha and -1 beta, IL-1 6, and matrix metalloproteinase-9. These findings indicate that HTLV-I -specific CD8(+) CTL are an important source of proinflammatory solubl e mediators that may contribute significantly to the pathogenesis of H AM/TSP.