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Mouse cytolytic T cells reactive with rat islet tumour RIN 5AH-B cells
1Hagedorn Research Laboratory, WHO Collaborating Centre for Research and Training on the Pathogenesis of Diabetes Mellitus, Gentofte, Denmark.
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.
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.