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
Y. Chernajovsky et al., 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, Gene therapy, 2(10), 1995, pp. 731-735
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.