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

Abstract

To investigate the pathogenic role of macrophage lineage (CD68+) cells in synovial proliferation in patients with human T cell leukemia virus I (HTLV-I) associated arthropathy (HAAP). Synovial tissues obtained from 3 patients with HAAP and 3 patients with osteoarthritis (OA) were examined for the expression of tumor necrosis 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 in HTLV-I infected synoviocytes. Changes in CD68+ cell population were examined by flow cytometric analysis. Proliferative effects of supernatants of HTLV-I infected synoviocytes on normal synoviocytes were also determined. TNF-alpha and HTLV-I tax/rex mRNA were preferentially expressed in CD68+ cells in HAAP synovia. Infection of OA synoviocytes by HTLV-I resulted 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 pathway. Our results suggest HTLV-I viral tropism for CD68+ cells, and that HTLV-I infected synoviocytes were induced to produce TNF-alpha, which enhances synovial proliferation in HAAP.