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 immunodeficiency (SCID) mice by spleen cells from diseased DBA/1 mice. The development of arthritis in SCID animals can be prevented by infection ex vivo of DBA/1 spleen cells with retroviruses expressing the monomeric soluble human p75 tumor necrosis factor (TNF) receptor (TNF-R). In addition, a vector engineered to express a polycystronic mRNA with TNF-R and the herpes simplex virus thymidine kinase (HSVtk) gene, while producing low levels of TNF-R, had a limited effect which could be blocked by treating the animals with ganciclovir. A retroviral vector expressing the HSVtk gene alone had no effect on this arthritis transfer model with or without ganciclovir. Serum levels of TNF-R did not correlate with clinical signs, however, lower anti-collagen antibody levels corresponded with lack of clinical symptoms. These results indicate that local production of cytokine inhibitor is essential for therapeutic purposes while systemic levels may not be required.
Chernajovsky
Y
Y
Sunley Division, Kennedy Institute of Rheumatology, London, UK.
Adams
G
G
Podhajcer
O L
OL
Mueller
G M
GM
Robbins
P D
PD
Feldmann
M
M
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control*; D002460:Cell Line; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy; D006801:Humans; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D012190:Retroviridae; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics; D013154:Spleen; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection
D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D003094:Collagen; D013937:Thymidine Kinase; D015774:Ganciclovir