Pathogenic lymphoid cells engineered to express TGF beta 1 ameliorate disease in a collagen-induced arthritis model.
Collagen-induced arthritis in DBA/1 mice is a model of rheumatoid arthritis with marked synovitis and erosions. The disease can be adoptively transferred to SCID mice with arthritogenic splenocytes from DBA/1 mice injected with bovine collagen type II. However, infection of arthritogenic splenocytes with a retrovirus expressing TGF beta 1 inhibits development of arthritis in SCID mice. When DBA/1 mice, at onset of arthritis have additional arthritogenic splenocytes transferred, exacerbation occurs, reflected in a rapid increase in the number of arthritic joints, increased paw swelling and higher levels of anti-collagen antibody. By infecting arthritogenic splenocytes ex vivo with TGF beta 1 retrovirus, this exacerbation was inhibited. TGF beta 1 was effective in lowering inflammation of joints with already established arthritis and inhibiting the spreading of the disease to other joints. Transient reduction in anti-collagen antibody levels could also be obtained using purified T cells infected with TGF beta 1 retrovirus. In addition, expression of TGF beta 1 in lymphocytes reduced the levels of gelatinase (MMP2) activity in inflamed joints.
Chernajovsky
Y
Y
Kennedy Institute of Rheumatology, Molecular Biology Laboratory, London, UK.
Adams
G
G
Triantaphyllopoulos
K
K
Ledda
M F
MF
Podhajcer
O L
OL
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D001323:Autoantibodies; D002478:Cells, Cultured; D003094:Collagen / Q000276:immunology; D018093:Gelatinases / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D012190:Retroviridae; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D001323:Autoantibodies; D016212:Transforming Growth Factor beta; D003094:Collagen; D018093:Gelatinases