INHIBITION OF TRANSFER OF COLLAGEN-INDUCED ARTHRITIS INTO SCID MICE BY EX-VIVO INFECTION OF SPLEEN-CELLS WITH RETROVIRUSES EXPRESSING SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR

Collagen-induced arthritis can be transferred into severe combined imm unodeficiency (SCID) mice by spleen cells from diseased DBA/1 mice. Th e development of arthritis in SCID animals can be prevented by infecti on ex vivo of DBA/1 spleen cells with retroviruses expressing the mono meric soluble human p75 tumor necrosis factor (TNF) receptor(TNF-R). I n addition, a vector engineered to express a polycystronic mRNA with T NF-R and the herpes simplex virus thymidine kinase (HSVtk) gene, while producing low levels of TNF-R, had a limited effect which could be bl ocked by treating the animals with ganciclovir. A retroviral vector ex pressing the HSVtk gene alone had no effect on this arthritis transfer model with or without ganciclovir. Serum levels of TNF-R did not corr elate with clinical signs, however, lower anti-collagen antibody level s corresponded with lack of clinical symptoms. These results indicate that local production of cytokine inhibitor is essential for therapeut ic purposes while systemic levels may not be required.