In vitro-generated regulatory T cells induced by Foxp3-retrovirus infection control murine contact allergy and systemic autoimmunity
| Autor: | Karin Loser, Jenny Apelt, Wiebke Hansen, Sandra Balkow, Stefan Beissert, Jan Buer |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Recombinant Fusion Proteins
CD40 Ligand Medizin Autoimmunity Mice Transgenic chemical and pharmacologic phenomena Biology Dermatitis Contact Kidney Lymphocyte Activation T-Lymphocytes Regulatory Mice Interleukin 21 Genetics Animals Cytotoxic T cell IL-2 receptor Antigen-presenting cell Molecular Biology Interleukin 3 Reverse Transcriptase Polymerase Chain Reaction FOXP3 Forkhead Transcription Factors Receptors Interleukin-2 hemic and immune systems Genetic Therapy Flow Cytometry Natural killer T cell Mice Inbred C57BL Retroviridae Desensitization Immunologic Antibodies Antinuclear CD4 Antigens Models Animal Immunology Interleukin 12 Molecular Medicine Female Retroviridae Infections T-Lymphocytes Cytotoxic |
| Zdroj: | Gene Therapy. 12:1294-1304 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/sj.gt.3302567 |
| Popis: | Regulatory T cells are promising candidates for the modulation of inflammation and autoimmunity. To generate regulatory T cells in vitro, we have infected nadie;ve CD4⁺CD25⁻ T cells with a retrovirus encoding the transcription factor Foxp3. Foxp3-infected T cells are similar to naturally occurring regulatory T cells as evidenced by surface marker expression and function. To investigate the effects of Foxp3-infected T cells on contact hypersensitivity (CHS) responses, sensitized mice were injected with Foxp3- or control virus-infected T cells. Only injection of Foxp3-infected T cells into sensitized mice significantly inhibited CHS compared to controls, indicating that Foxp3-infected T cells are suppressive in vivo. These findings prompted treatment of autoimmune-prone CD40L transgenic (tg) mice, which develop a severe systemic autoimmune disease including autoreactive T cells and autoantibodies, with Foxp3-infected T cells. Interestingly, injections of Foxp3-infected T cells into CD40L tg mice inhibited the ongoing development of autoimmune dermatitis and activation of cytotoxic CD8⁺ T cells. Strikingly, treatment with Foxp3-infected T cells reduced serum concentrations of antinuclear antibodies in CD40L tg mice, which was paralleled with reduced renal immunoglobulin depositions and increased kidney function. Together, these findings indicate that newly in vitro-generated regulatory T cells can be successfully used to treat inflammatory and ongoing autoimmune disorders. © 2005 Nature Publishing Group All rights reserved. |
| Databáze: | OpenAIRE |
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