Mouse cytolytic T cells reactive with rat islet tumour RIN 5AH-B cells.
Insulin dependent (type 1) diabetes mellitus is considered to be an autoimmune disease characterized by a specific destruction of the insulin-producing pancreatic beta cells. We have explored the possibilities of raising T cells specific for putative pancreatic beta-cell autoantigens using a xenogeneic system. Mouse T cells were induced against the rat insulinoma cells RIN 5AH-B (RIN) and tested for their specific reactivity. No MHC class II-restricted beta-cell-specific helper T-cell reactivity could be detected within the bulk cultures as measured by proliferation, but a remarkably high cytotoxicity against the RIN cells was observed. The target antigen on the cell surface recognized by the generated cytotoxic T cells was shown to be the rat class I major histocompatibility antigen RT1g, and not a beta-cell or tumour cell-specific antigen associated with RIN cell MHC molecules. Our results demonstrate that it is feasible to evoke a xenogeneic T-cell response against the RIN cells. However, the mouse T cells recognize a dominant epitope present on the expressed rat class I major histocompatibility antigen RT1Ag and not a beta-cell-specific antigen. Hence, we conclude that it appears most unlikely that beta-cell-specific T cells can be raised in the xenogeneic system.
Schøller
J
J
Hagedorn Research Laboratory, WHO Collaborating Centre for Research and Training on the Pathogenesis of Diabetes Mellitus, Gentofte, Denmark.
Rubin
B
B
D000818:Animals; D002478:Cells, Cultured; D002860:Chromium Radioisotopes; D006649:Histocompatibility Antigens / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014407:Tumor Cells, Cultured
D002860:Chromium Radioisotopes; D006649:Histocompatibility Antigens