Bone marrow-derived cells are responsible for the development of autoimmune arthritis in human T cell leukemia virus type I-transgenic mice and those of normal mice can suppress the disease.
Previously, we reported that human T cell leukemia virus type I env-pX region-introduced transgenic (pX-Tg) mice developed an inflammatory polyarthropathy associated with a development of autoimmunity. To elucidate roles of autoimmunity in the development of arthritis, the immune cells were reciprocally replaced between pX-Tg mice and non-transgenic (Tg) mice. When bone marrow (BM) cells and spleen cells from pX-Tg mice were transferred into irradiated non-Tg mice, arthritis developed in these mice. In contrast, arthritis in pX-Tg mice was completely suppressed by non-Tg BM and spleen cells. Similar results were obtained with BM cells only. After the transplantation, T cells, B cells, and macrophages were replaced completely, whereas cells in the joints were replaced partially. In those mice, serum Ig and rheumatoid factor levels correlated with the disease development, and inflammatory cytokine expression was elevated in the arthritic joints. Furthermore, involvement of T cells in the joint lesion was suggested, because the incidence was greatly reduced in athymic nu/nu mice although small proportion of the mice still developed arthritis. These observations suggest that BM stem cells are abnormal, causing autoimmunity in pX-Tg mice, and this autoimmunity plays an important, but not absolute, role in the development of arthritis in this Tg mouse.
Saijo
S
S
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Japan.
Kotani
M
M
Habu
K
K
Ishitsuka
C
C
Yamamoto
H
H
Sekiguchi
T
T
Iwakura
Y
Y
D019264:Adoptive Transfer; D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000517:prevention & control; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007596:Joints / Q000378:metabolism / Q000821:virology; D008221:Lymphoid Tissue / Q000378:metabolism / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D011828:Radiation Chimera / Q000276:immunology; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D012217:Rheumatoid Factor / Q000097:blood; D014157:Transcription Factors; D019076:Transgenes / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins
D016207:Cytokines; D007136:Immunoglobulins; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D014759:Viral Envelope Proteins; D054334:Viral Regulatory and Accessory Proteins; C072343:pX protein, Human T-lymphotropic virus 1; D012217:Rheumatoid Factor