title: Pathogenic lymphoid cells engineered to express TGF beta 1 ameliorate disease in a collagen-induced arthritis model.
abstract: 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.
authors.affiliation: Kennedy Institute of Rheumatology, Molecular Biology Laboratory, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Chernajovsky
authors.forename: G
authors.initials: G
authors.lastname: Adams
authors.forename: K
authors.initials: K
authors.lastname: Triantaphyllopoulos
authors.forename: M F
authors.initials: MF
authors.lastname: Ledda
authors.forename: O L
authors.initials: OL
authors.lastname: Podhajcer
mesh_terms: 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*
chemical_list: D001323:Autoantibodies; D016212:Transforming Growth Factor beta; D003094:Collagen; D018093:Gelatinases