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Myoblasts fail to stimulate T cells but induce tolerance
A N Warrens1, J Y Zhang, S Sidhu
1Department of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
International Immunology
|June 1, 1994
Summary
Myoblasts, used in gene therapy, may not trigger immune responses. This study found that myoblast-like cells expressing HLA-DR1 did not stimulate T cells, suggesting they lack necessary costimulatory signals for immune activation.
Area of Science:
- Immunology
- Cell Biology
- Gene Therapy
Background:
- Myoblast transfer and gene therapy necessitate understanding myoblast immunogenicity.
- Producing pure myoblast populations is challenging.
- A tumor-derived muscle cell line (TE671) with myoblast features was used.
Purpose of the Study:
- To investigate the immunogenicity of myoblasts, particularly their ability to stimulate T cells.
- To determine if myoblasts expressing HLA-DR1 can initiate allogeneic or neoantigen-specific immune responses.
Main Methods:
- Transfected TE671 cell line to express HLA-DR1.
- Assessed T cell stimulation using HLA-DR1-specific T cell clones and primary alloresponse.
- Tested antigen presentation of HA 306-324 peptide to DR1-restricted T cells.
- Evaluated T cell tolerance induction after preincubation with TE671 and peptide.
Main Results:
- HLA-DR1-expressing TE671 cells failed to stimulate established T cell clones or primary alloresponses.
- TE671 cells could not present HA 306-324 peptide to relevant T cell clones.
- Preincubation with TE671 and peptide induced T cell tolerance.
Conclusions:
- Myoblasts may lack essential costimulatory signals for T cell activation.
- Myoblast transplantation is unlikely to stimulate allospecific T cells.
- In vivo transfection with myoblasts may not initiate neoantigen-specific immune responses.