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Myoblasts fail to stimulate T cells but induce tolerance
Authors:Warrens, Anthony N.   Zhang, Jun Yan   Sidhu, Sid   Watt, Diana J   Lombardi, Giovanna   Sewry, Caroline A   Lechler, Robert I.
Affiliation:1 Department of immunology London W12 ONN, UK
2 Neuromuscular Unit, Royal Postgraduate Medical School, Hammersmith Hospital London W12 ONN, UK
3 Department of Anatomy, Charing Cross and Westminster Medical School London W6 8RP, UK
Abstract:Recent interest in myoblast transfer and in the use of myoblastsas vehicles in gene therapy has made it important to understandthe potential immunogenicity of allogeneic or neoantlgen-expresslngmyoblasts. Given the problems of producing a pure populationof myoblasts, In this study we used a tumour-derived musclecell line (TE671), with phenotyplc features of myoblasts, whichwe transfected to express HLA-DR1. However, this cell line wasunable to stimulate either established HLA-DR1-specific alloreactlveT cell clones or a primary alloresponse. Nor could it presenthaemagglutlnln peptide HA 306–324 to DR1-restricted, HA306–324-speciflc T cell clones or lines. Indeed, prelncubatlonwith DR1-expressing TE671 and HA 306–324 rendered suchT cells tolerant as Judged by their subsequent inability toproliferate in response to a DR1+ B cell line plus peptide HA306–324. These results imply that myoblasts do not providecostlmulatory signals, and are therefore unlikely to stimulateallospeclfic T cells following myoblasts transplantation orto initiate neoantlgen-speclfic immune responses following Invivo transfection.
Keywords:allograft rejection   gene therapy   immunogenicity   muscular dystrophy   myogenic cells
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