Molecular Immunology 45 (2008) 3526–3535
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Molecular Immunology
journal homepage: www.elsevier.com/locate/molimm
Cartilage proteoglycan-specic T cells as vectors of immunomodulatory biologicals in chronic proteoglycan-induced arthritis
Teun Guichelaar a,b , Corlinda B. ten Brink a , Peter J. van Kooten a , Suzanne E. Berlo a , Floris P. Lafeber c , Chris. P. Broeren a , Willem van Eden a , Femke Broere a,
a b c
Division of Immunology, Department of Infectious Diseases and Immunology, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands
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Systemic administration of agents that neutralize or antagonize Th 1-mediated pro-inammatory responses has been demonstrated to ameliorate inammation in chronic autoimmune disease. However, systemic administration of such immunosuppressive biologicals causes serious side effects and has only limited success. To minimize these side effects, autoantigen-specic lymphocytes have been proposed as a carrier to deliver immunosuppressive agents to sites of inammation. Here we studied the effects of primary cartilage proteoglycan-specic CD4+ T cells that were transduced using an efcient method of viral transduction with active genes encoding IL-1 receptor antagonist, soluble TNF- receptor-Ig, IL-4 or IL-10 in chronic proteoglycan-induced arthritis in mice. This is the rst study describing such gene therapy using primary CD4+ T cells in a chronic arthritis. Moreover, the impact of proteoglycan-specic Th 1, Th 2 or na¨ve T cells was studied. Although proteoglycan-TCR transgenic CD4+ T cells can transfer arthritis to lymphopenic recipients, none of the proteoglycan-TCR transgenic T cell phenotypes that were tested induced worsening of arthritis in wild type hosts. Proteoglycan-specic T cells ameliorated arthritis when expressing the transduced IL-10 gene, and not when expressing the other transgenes/phenotypes. Although all of the tested biologicals can suppress in a wide range of different inammatory disorders, especially IL-10 would therefore serve as a promising candidate to be used in cellular gene therapy for chronic arthritis. 2008 Elsevier Ltd. All rights reserved.

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