PATHOGENIC LYMPHOID-CELLS ENGINEERED TO EXPRESS TGF-BETA-1 AMELIORATEDISEASE IN A COLLAGEN-INDUCED ARTHRITIS MODEL

Collagen-induced arthritis in DBA/1 mice is a model of rheumatoid arth ritis with marked synovitis and erosions. The disease can be adoptivel y transferred to SCID mice with arthritogenic splenocytes from DBA/1 m ice injected with bovine collagen type II. However, infection of arthr itogenic splenocytes with a retrovirus expressing TGF beta 1 inhibits development of arthritis in SCID mice. When DBA/1 mice, at onset of ar thritis have additional arthritogenic splenocytes transferred, exacerb ation occurs, reflected in a rapid increase in the number of arthritic joints, increased paw swelling and higher levels of anti-collagen ant ibody. By infecting arthritogenic splenocyte ex vivo with TGF beta 1 r etrovirus, this exacerbation was inhibited. TGF beta 1 was effective-i n lowering inflammation of joints with already established arthritis a nd inhibiting the spreading of the dis-ease to other joints. Transient reduction in anti-collagen antibody levels could also be obtained usi ng purified T cells infected with TGF beta 1 retrovirus. In addition, expression of TGF beta 1 in lymphocytes reduced the levels of gelatina se (MMP2) activity in inflamed joints.