Modulation of MHC class II antigen expression in human myoblasts after treatment with IFN-γ

Mantegazza, R. MD
Hughes, S. M. PhD
Mitchell, D. MS
Travis, M. MS
Blau, H. M. PhD; and
Steinman, L. MD

Departments of Neurology and Neurological Sciences (Drs. Mantegazza and Steinman, and D. Mitchell), and Pharmacology (Drs. Hughes and Blau, and M. Travis), Stanford University, Stanford, CA, and Department of Neuromuscular Diseases (Dr. Mantegazza), Istituto Neurologico “C. Besta,” Milan, Italy.

Address correspondence and reprint requests to Dr. Lawrence Steinman, Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA 94305-5235.

Renato Mantegazza is a recipient of a Patty Roach Fellowship from the California Chapter of the Myasthenia Gravis Foundation, and is on leave from the Istituto Neurologico “C. Besta,” Milan, Italy. Supported by grants from Smith Kline, Beckman, the National Institutes of Health, and the Muscular Dystrophy Association.

Received June 5, 1990. Accepted for publication in final form December 11, 1990.

Neurology 41(7):p 1128-1132, July 1991.

Article abstract

Some investigators have proposed myoblast transfer as a potential therapy for the treatment of Duchenne muscular dystrophy. Little is known about the immunobiology of myoblast transplantation. Transplantation rejection is mediated to a large extent by CD8+ T cells, which recognize alloantigens encoded by class IHL A genes, and by CD4+ T cells, which recognize alloantigens encoded by class II HLA genes. Gamma interferon (IFN-γ) is a potent inducer of HLA class II molecules as well as β₂-microglobulin, which is co-expressed with HLA class I. IFN-γ may be a critical cytokine involved in graft rejection. We purified human myoblasts by flow cytometry and incubated them in vitro for varying time periods with recombinant human IFN-γ. The inducibility of HLA-DR and -DP molecules raises a note of caution concerning possible rejection phenomenon which might occur following myoblast transplantation.