Synovial hyperplasia in HTLV-I associated arthropathy is induced by tumor necrosis factor-alpha produced by HTLV-I infected CD68+cells

Objective. To investigate the pathogenic role of macrophage Lineage (CD68+) cells in synovial proliferation in patients with human T cell leukemia vir us I (HTLV-I) associated arthropathy (HAAP). Methods. Synovial tissues obtained from 3 patients with HAAP and 3 patients with osteoarthritis (OA) were examined for the expression of tumor necrosi s factor-alpha (TNF-alpha) mRNA, HTLV-I tax/rex mRNA, and number of CD68 by in situ reverse transcription assay and immunohistochemistry. Western blot and flow cytometric analyses were used to determine TNF-alpha production i n HTLV-I infected synoviocytes. Changes in CD68+ cell population were exami ned by flow cytometric analysis. Proliferative effects of supernatants of H TLV-I infected synoviocytes on normal synoviocytes were also determined. Results. TNF-alpha and HTLV-I tax/rex mRNA were preferentially expressed in CD68+ cells in HAAP synovia. Infection of OA synoviocytes by HTLV-I result ed in preferential expression in CD68+ cells, and these cells produced TNF- alpha. Supernatants of HTLV-I infected synoviocytes significantly enhanced the proliferation of normal synoviocytes through a TNF-alpha, dependent pat hway. Conclusion, Our results suggest HTLV-I viral tropism for CD68+ cells, and t hat HTLV-I infected synoviocytes were induced to produce TNF-alpha, which e nhances synovial proliferation in HAAP.