title: Myoblasts fail to stimulate T cells but induce tolerance.
abstract: Recent interest in myoblast transfer and in the use of myoblasts as vehicles in gene therapy has made it important to understand the potential immunogenicity of allogeneic or neoantigen-expressing myoblasts. Given the problems of producing a pure population of myoblasts, in this study we used a tumour-derived muscle cell line (TE671), with phenotypic features of myoblasts, which we transfected to express HLA-DR1. However, this cell line was unable to stimulate either established HLA-DR1-specific allorective T cell clones or a primary alloresponse. Nor could it present haemagglutinin peptide HA 306-324 to DR1-restricted, HA 306-324-specific T cell clones or lines. Indeed, preincubation with DR1-expressing TE671 and HA 306-324 rendered such T cells tolerant as judged by their subsequent inability to proliferate in response to a DR1+ B cell line plus peptide HA 306-324. These results imply that myoblasts do not provide costimulatory signals, and are therefore unlikely to stimulate allospecific T cells following myoblasts transplantation or to initiate neoantigen-specific immune responses following in vivo transfection.
authors.affiliation: Department of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
authors.forename: A N
authors.initials: AN
authors.lastname: Warrens
authors.forename: J Y
authors.initials: JY
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Sidhu
authors.forename: D J
authors.initials: DJ
authors.lastname: Watt
authors.forename: G
authors.initials: G
authors.lastname: Lombardi
authors.forename: C A
authors.initials: CA
authors.lastname: Sewry
authors.forename: R I
authors.initials: RI
authors.lastname: Lechler
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D002999:Clone Cells; D015798:HLA-DR1 Antigen / Q000235:genetics; D006388:Hemagglutinins / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009132:Muscles / Q000166:cytology* / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D015798:HLA-DR1 Antigen; D006388:Hemagglutinins; D007376:Interleukin-2