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Collagen II-pulsed antigen-presenting cells genetically modified to secrete IL-4 down-regulate collagen-induced arthritis

Gene Therapy volume 8, pages 1855–1862 (2001)Cite this article

Abstract

We explored the possibility that pulsed antigen-presenting cells (APC) provide a model vector system for site-specific delivery of immunosuppressive proteins during collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis. Thus, mice were treated with either B cells or macrophages engineered to secrete IL-4 and loaded (or not) with type II collagen (CII). Systemic injection of an IL-4-producing B cell hybridoma resulted in a reduction of arthritis severity which was further improved when APC were incubated with CII before their transfer. Unmanipulated B cells loaded with CII also exerted a potent suppressive effect. Likely, clinical amelioration was observed in mice given at priming syngeneic bone marrow-derived macrophages producing IL-4 and pulsed with CII in comparison to the other groups. When the same dose of cells was transferred at disease onset, a moderate beneficial effect was observed. Whatever the APC inoculated, the beneficial effect did not rely upon an IL-4-driven shift towards Th2 phenotype. Systemic administration of fluorescent dye labeled macrophages to arthritic mice has shown that some of these cells rapidly migrate to joints. Moreover, IL-4 transfected macrophages retained their potent capacity to present CII peptides to T cells. These findings validate the use of CII peptide-loaded engineered APC as therapeutic vector cells in CIA and allow consideration of this strategy for the administration of various anti-inflammatory proteins.

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Acknowledgements

The authors are indebted to Sylvie Mistou and Franck Lager for their excellent technical assistance. This work was supported in part by the Association de Recherche sur la Polyarthrite (ARP) and institutional grants from Institut National de la Santé et de la Recherche Médicale (INSERM).

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Authors and Affiliations

  1. INSERM U477, Université René Descartes, Paris, France

    L Guéry, G Chiocchia, F Batteux & C Fournier

  2. Laboratoire d'Immunologie, Hôpital Cochin, Paris, France

    F Batteux

  3. UPRES EA-2361 and Hôpital Avicenne (AP-HP), Université Léonard de Vinci, Bobigny, France

    M-C Boissier

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  1. L Guéry
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  2. G Chiocchia
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  4. M-C Boissier
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  5. C Fournier
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Guéry, L., Chiocchia, G., Batteux, F. et al. Collagen II-pulsed antigen-presenting cells genetically modified to secrete IL-4 down-regulate collagen-induced arthritis. Gene Ther 8, 1855–1862 (2001). https://doi.org/10.1038/sj.gt.3301613

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  • DOI: https://doi.org/10.1038/sj.gt.3301613

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