Human T Cell Leukemia Virus Type I (Htlv-1)-Specific Cd8(+) Ctl Clones From Patients With Htlv-I-Associated Neurologic Disease Secrete Proinflammatory Cytokines, Chemokines, and Matrix Metalloproteinase

Human T cell leukemia virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neurologic disease characterized by marked degeneration of the spinal cord and the presence of infiltrating CD8(+) T cells and macrophages, HAM/TSP patients have very high frequencies of HTLV-I-specific CD8(+) CTL in peripheral 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 potential role of soluble mediators secreted by CD8(+) T cells in the pathogenesis 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 secrete cytokines, chemokines, and matrix metalloproteinases. The results demonstrate that the majority of these CTL clones secrete IFN-gamma, TNF-alpha, macrophage-inflammatory protein-1 alpha and -1 beta, IL-16, and matrix metalloproteinase-9. These findings indicate that HTLV-I-specific CD8(+) CTL are an important source of proinflammatory soluble mediators that may contribute significantly to the pathogenesis of HAM/TSP. [References: 50]

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