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*
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15261; and
Seoul National University, Seoul, Korea
Dendritic cells (DC) are APCs that are able to stimulate or inhibit
immune responses, depending on levels of expression of MHC class I and
II costimulatory molecules and cytokines. Our previous studies have
suggested that the observed contralateral effect, where injection of a
vector carrying certain immunomodulatory genes into one joint resulted
in inhibition of arthritis in untreated joints, is mediated by in vivo
modification of DC. Therefore, we have examined the ability of
genetically modified DC to suppress established murine collagen-induced
arthritis (CIA) after i.v. delivery. IL-4 has been shown to partially
reduce the severity of CIA after repeated injection of recombinant
protein or by injection of an adenoviral vector expressing IL-4. Here
we demonstrate that i.v. injection of immature DC, infected with an
adenoviral vector expressing IL-4, into mice with established CIA
resulted in almost complete suppression of disease, with no recurrence
for up to 4 wk posttreatment. Injection i.v. of fluorescently labeled
DC demonstrated that the cells rapidly migrated to the liver and spleen
after 6 h and to the lymph nodes by 24 h. In culture, spleen
cells from DC/IL-4-treated mice produced less IFN-
after stimulation
by collagen than did control groups. In addition, DC/IL-4
administration decreased the level of specific Abs against type II
collagen, in particular the IgG2 Th1 isotype 14 days posttreatment.
These results demonstrate the ability to treat effectively established
murine arthritis by systemic administration of DC expressing
IL-4.
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