Reestablishment of tolerance induction in
rheumatoid arthritis (RA) would be an optimal treatment with few, if any, side effects. However, to develop such a treatment further insights in the immunological mechanisms governing tolerance are needed. We have developed a model of
antigen-specific tolerance in
collagen type II (CII) induced
arthritis (CIA) using lentivirus-based gene therapy. The
immunodominant epitope of CII was inserted into a lentivirus vector to achieve expression on the
MHC class II molecule and the lentiviral particles were subsequently intravenously injected at different time points during CIA. Injection of lentiviral particles in early phases of CIA, that is, at day 7 or day 26 after CII immunisation, partially prevented development of
arthritis, decreased the serum levels of CII-specific
IgG antibodies, and enhanced the suppressive function of CII-specific T regulatory cells. When lentiviral particles were injected during manifest
arthritis, that is, at day 31 after CII immunisation, the severity of
arthritis progression was ameliorated, the levels of CII-specific
IgG antibodies decreased and the proportion of T regulatory cells increased. Thus,
antigen-specific gene therapy is effective when administered throughout the inflammatory course of
arthritis and offers a good model for investigation of the basic mechanisms during tolerance in CIA.