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 virus 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 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.


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 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.


CONCLUSIONS
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.
Yin
W
W
Rheumatology, Immunology and Genetics Program, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
Hasunuma
T
T
Kobata
T
T
Sumida
T
T
Nishioka
K
K
D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D002455:Cell Division / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015490:HTLV-I Infections / Q000276:immunology / Q000473:pathology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D006965:Hyperplasia; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000473:pathology / Q000821:virology*; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D012333:RNA, Messenger; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule