Bone marrow cells carrying the env-pX transgene play a role in the severity but not prolongation of arthritis in human T-cell leukaemia virus type-I transgenic rats: a possible role of articular tissues carrying the transgene in the prolongation of arthritis.
Transgenic rats carrying the env-pX gene of human T-cell leukaemia virus type-I (env-pX rats) were immunized with type II collagen (CII), and chronological alterations of arthritis were compared with findings of collagen-induced arthritis (CIA) in wildtype Wistar-King-Aptekman-Hokudai (WKAH) rats. Arthritis induced by CII in env-pX rats was more severe and persisted longer than CIA in WKAH rats. To determine whether the phenomenon is caused mainly by the transgene-carrying lymphocytes or articular tissues, we immunized lethally irradiated env-pX and WKAH rats with reciprocal bone marrow cell (BMC) transplantation. A severe but transient arthritis was induced by CII in WKAH rats reconstituted by env-pX BMC (w/tB/CII rats). On the other hand, in env-pX rats reconstituted by WKAH BMC, arthritis persisted longer than in w/tB/CII rats, although the degree was less at an early phase after CII immunization. These findings suggest that articular tissues rather than the BMCs carrying the env-pX transgene play a role in the prolongation of arthritis in env-pX rats, although BMCs carrying the transgene are associated with the severity of arthritis. When inflammatory cytokines in synovial cells isolated from env-pX rats before they developed arthritis were examined, interleukin-6 (IL-6) was detected at a higher level than in synovial cells from WKAH rats, thus suggesting the critical role of IL-6 in env-pX arthritis.
Department of Pathology/Pathophysiology, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Asami
A
Abe
Akihiro
A
Ishizu
Hitoshi
H
Ikeda
Hiroko
H
Hayase
Takahiro
T
Tsuji
Yukiko
Y
Miyatake
Muneharu
M
Tsuji
Kazunori
K
Fugo
Toshiaki
T
Sugaya
Masato
M
Higuchi
Takeo
T
Matsuno
Takashi
T
Yoshiki
D000818:Animals; D030801:Animals, Genetically Modified; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015686:Gene Products, env / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics*; D019076:Transgenes; D054334:Viral Regulatory and Accessory Proteins
D015686:Gene Products, env; D015850:Interleukin-6; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C072343:pX protein, Human T-lymphotropic virus 1