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. 1990 Mar;136(3):503–508.

Induction of HLA-DR expression on human myoblasts with interferon-gamma.

R Hohlfeld 1, A G Engel 1
PMCID: PMC1877498  PMID: 2107747

Abstract

Myoblast transplantation is an experimental therapy that may be useful in hereditary muscle diseases. One obstacle to this approach is immune rejection. We evaluated human myoblasts and myotubes for surface expression of HLA class I and II histocompatibility antigens. The myoblast preparations, cultured from muscle biopsy specimens, were more than 95% pure as assessed by immunostaining with the Leu19 monoclonal antibody that reacts with human myoblasts and regenerating muscle fibers. Myoblasts and myotubes constitutively expressed HLA-class I but not HLA-class II molecules. However, HLA-class II expression was induced on mononucleated myoblasts after culture for 5 days in the presence of recombinant human interferon-gamma. The results indicate that transplanted myoblasts can be rejected because of histoincompatibility at the HLA-class I and HLA class II locus. Furthermore, an aberrant expression of HLA-class II antigen on myoblasts in vivo may play a role in the pathogenesis of autoimmune muscle disorders.

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Selected References

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  1. Blau H. M., Webster C. Isolation and characterization of human muscle cells. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5623–5627. doi: 10.1073/pnas.78.9.5623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bottazzo G. F., Todd I., Mirakian R., Belfiore A., Pujol-Borrell R. Organ-specific autoimmunity: a 1986 overview. Immunol Rev. 1986 Dec;94:137–169. doi: 10.1111/j.1600-065X.1986.tb01168.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Durum S. K., Schmidt J. A., Oppenheim J. J. Interleukin 1: an immunological perspective. Annu Rev Immunol. 1985;3:263–287. doi: 10.1146/annurev.iy.03.040185.001403. [DOI] [PubMed] [Google Scholar]
  4. Emslie-Smith A. M., Arahata K., Engel A. G. Major histocompatibility complex class I antigen expression, immunolocalization of interferon subtypes, and T cell-mediated cytotoxicity in myopathies. Hum Pathol. 1989 Mar;20(3):224–231. doi: 10.1016/0046-8177(89)90128-7. [DOI] [PubMed] [Google Scholar]
  5. Forsum U., Claesson K., Hjelm E., Karlsson-Parra A., Klareskog L., Scheynius A., Tjernlund U. Class II transplantation antigens: distribution in tissues and involvement in disease. Scand J Immunol. 1985 May;21(5):389–396. doi: 10.1111/j.1365-3083.1985.tb01823.x. [DOI] [PubMed] [Google Scholar]
  6. Gutmann D. H., Fischbeck K. H. Molecular biology of Duchenne and Becker's muscular dystrophy: clinical applications. Ann Neurol. 1989 Aug;26(2):189–194. doi: 10.1002/ana.410260202. [DOI] [PubMed] [Google Scholar]
  7. Hall B. M., Bishop G. A., Duggin G. G., Horvath J. S., Philips J., Tiller D. J. Increased expression of HLA-DR antigens on renal tubular cells in renal transplants: relevance to the rejection response. Lancet. 1984 Aug 4;2(8397):247–251. doi: 10.1016/s0140-6736(84)90297-6. [DOI] [PubMed] [Google Scholar]
  8. Hohlfeld R. Neurological autoimmune disease and the trimolecular complex of T-lymphocytes. Ann Neurol. 1989 Jun;25(6):531–538. doi: 10.1002/ana.410250602. [DOI] [PubMed] [Google Scholar]
  9. Karpati G., Pouliot Y., Carpenter S. Expression of immunoreactive major histocompatibility complex products in human skeletal muscles. Ann Neurol. 1988 Jan;23(1):64–72. doi: 10.1002/ana.410230111. [DOI] [PubMed] [Google Scholar]
  10. Karpati G., Pouliot Y., Zubrzycka-Gaarn E., Carpenter S., Ray P. N., Worton R. G., Holland P. Dystrophin is expressed in mdx skeletal muscle fibers after normal myoblast implantation. Am J Pathol. 1989 Jul;135(1):27–32. [PMC free article] [PubMed] [Google Scholar]
  11. Mandel J. L. Dystrophin. The gene and its product. Nature. 1989 Jun 22;339(6226):584–586. doi: 10.1038/339584a0. [DOI] [PubMed] [Google Scholar]
  12. Mason D. W., Morris P. J. Effector mechanisms in allograft rejection. Annu Rev Immunol. 1986;4:119–145. doi: 10.1146/annurev.iy.04.040186.001003. [DOI] [PubMed] [Google Scholar]
  13. Milton A. D., Fabre J. W. Massive induction of donor-type class I and class II major histocompatibility complex antigens in rejecting cardiac allografts in the rat. J Exp Med. 1985 Jan 1;161(1):98–112. doi: 10.1084/jem.161.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Parham P. MHC molecules. A profitable lesson in heresy. Nature. 1989 Aug 10;340(6233):426–428. doi: 10.1038/340426a0. [DOI] [PubMed] [Google Scholar]
  15. Partridge T. A., Morgan J. E., Coulton G. R., Hoffman E. P., Kunkel L. M. Conversion of mdx myofibres from dystrophin-negative to -positive by injection of normal myoblasts. Nature. 1989 Jan 12;337(6203):176–179. doi: 10.1038/337176a0. [DOI] [PubMed] [Google Scholar]
  16. Pober J. S. Warner-Lambert/Parke-Davis award lecture. Cytokine-mediated activation of vascular endothelium. Physiology and pathology. Am J Pathol. 1988 Dec;133(3):426–433. [PMC free article] [PubMed] [Google Scholar]
  17. Ritz J., Schmidt R. E., Michon J., Hercend T., Schlossman S. F. Characterization of functional surface structures on human natural killer cells. Adv Immunol. 1988;42:181–211. doi: 10.1016/s0065-2776(08)60845-7. [DOI] [PubMed] [Google Scholar]
  18. Sandvig S., Laskay T., Andersson J., De Ley M., Andersson U. Gamma-interferon is produced by CD3+ and CD3- lymphocytes. Immunol Rev. 1987 Jun;97:51–65. doi: 10.1111/j.1600-065x.1987.tb00516.x. [DOI] [PubMed] [Google Scholar]
  19. Schubert W., Zimmermann K., Cramer M., Starzinski-Powitz A. Lymphocyte antigen Leu-19 as a molecular marker of regeneration in human skeletal muscle. Proc Natl Acad Sci U S A. 1989 Jan;86(1):307–311. doi: 10.1073/pnas.86.1.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wadgymar A., Urmson J., Baumal R., Halloran P. F. Changes in Ia expression in mouse kidney during acute graft-vs-host disease. J Immunol. 1984 Apr;132(4):1826–1832. [PubMed] [Google Scholar]
  21. Wekerle H., Schwab M., Linington C., Meyermann R. Antigen presentation in the peripheral nervous system: Schwann cells present endogenous myelin autoantigens to lymphocytes. Eur J Immunol. 1986 Dec;16(12):1551–1557. doi: 10.1002/eji.1830161214. [DOI] [PubMed] [Google Scholar]

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