Induction of primary immune responses by allogeneic human myoblasts: dissection of the cell types required for proliferation, IFNgamma secretion and cytotoxicity.
Non-professional antigen-presenting cells (APC) have a limited ability to activate T lymphocytes during normal and auto-immune responses. Myoblasts could play an important role as APC in the etiology of autoimmune myasthenia gravis and polymyositis, as well as during muscle graft rejection. We examined the role of different component cell subsets in the response of human peripheral blood mononuclear cells (PBMC) to allogeneic myoblasts. Treatment of myoblasts with TNFalpha or IFNgamma led to the expression of a range of immunostimulatory molecules including MHC class I and II, and CD95 (Fas), but not B7 family molecules. Whole PBMC, cultured with allogeneic myoblasts, proliferated, secreted IFNgamma, and were cytotoxic. Proliferation and IFNgamma secretion were largely dependent on the presence of CD4+ lymphocytes, but neither CD4+ nor CD8+ T cells were responsible for cytotoxicity, which was mediated by MHC class II+ non-T mononuclear cells. However, purified CD4+ lymphocytes co-cultured with allogeneic myoblasts required co-stimulation with anti-CD28 antibodies for proliferation and IFNgamma secretion, which only induced a low level of IFNgamma secretion by CD8+ lymphocytes and did not induce cytotoxic function. These results suggest that human myoblasts can act as antigen-presenting cells for naive T lymphocytes, but only with additional co-stimulation.
Curnow
S J
SJ
Neurosciences Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK. john.curnow@imm.ox.ac.uk
Willcox
N
N
Vincent
A
A
D017951:Antigen Presentation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000276:immunology; D009157:Myasthenia Gravis / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000276:immunology*; D017285:Polymyositis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma