Myoblast transplantation in monkeys: control of immune response by FK506
| Autor: | Marlyne Goulet, Brigitte Roy, Francine J. Dugré, Claude Gravel, I. Kinoshita, Raynald Roy, Jacques P. Tremblay, Isabelle Asselin |
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| Rok vydání: | 1996 |
| Předmět: |
Macrophage colony-stimulating factor
Interleukin 2 medicine.medical_treatment Molecular Sequence Data Muscle Fibers Skeletal Biology Polymerase Chain Reaction Tacrolimus Pathology and Forensic Medicine Cellular and Molecular Neuroscience Immune system Transforming Growth Factor beta Chlorocebus aethiops medicine Myocyte Animals RNA Messenger Muscle Skeletal Base Sequence Myogenesis Interleukin-6 Glyceraldehyde-3-Phosphate Dehydrogenases Granulocyte-Macrophage Colony-Stimulating Factor Immunosuppression General Medicine Macaca mulatta Transplantation Granzyme B Neurology Immunology Interleukin-2 Neurology (clinical) Immunosuppressive Agents medicine.drug |
| Zdroj: | Journal of neuropathology and experimental neurology. 55(6) |
| ISSN: | 0022-3069 |
| Popis: | Myoblasts were grown from monkey muscle biopsies and infected in vitro with a defective retroviral vector containing a cytoplasmic beta-galactosidase (beta-gal) gene. These myoblasts were then transplanted to 14 different monkeys, 6 of which were immunosuppressed with FK506. Without immunosuppression, only a few myoblasts and myotubes expressing beta-gal were observed 1 week after the transplantation, but no cells expressing beta-gal were observed after 4 weeks. This result was attributed to immune responses since infiltration by CD4+ or CD8+ lymphocytes was abundant 1 week after transplantation but not after 4 weeks. The expression of interleukin 6 (IL-6), interleukin 2 (IL-2), granulocyte/macrophage colony stimulating factor (GM-CSF), transforming growth factor-beta (TGF-beta) and granzyme B mRNAs was increased in the myoblast-injected muscle indicating that the infiltrating lymphocytes were activated. Moreover, antibodies against the donor myoblasts were detected in 3 out of 6 cases. When the monkeys were immunosuppressed with FK506, muscle fibers expressing beta-galactosidase (beta-gal) were present 1, 4 and 12 weeks after the transplantation. There was neither significant infiltration by CD4 or CD8 lymphocytes, nor antibodies detected. The mRNA expression of most cytokines was significantly reduced as compared to the nonimmunosuppressed monkeys. These results indicate that FK506 is effective in controlling short-term immune reactions following myoblast transplantation in monkeys and suggest that it may prove useful for myoblast transplantation in Duchenne Muscular Dystrophy patients. |
| Databáze: | OpenAIRE |
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