MYOBLASTS FAIL TO STIMULATE T-CELLS BUT INDUCE TOLERANCE

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 alloreactive 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.