β-cell damage in TNF/CD80 transgenic mice. Electron micrographs of damaged β cells in either TNF/CD80 double transgenic mice (A–C) or in transgenic mutant mice lacking either a functional perforin gene (D) or a normal TNF-LTα locus (E). Damaged β cells show lesions of submembranous focal apoptosis with dilation of ER cavities limited at the points of contact with activated lymphocytes (A and B, arrows) or extended throughout the whole cytoplasm (C, arrowheads, D and E) together with swelling of mitochondria (C, arrow). There is neither chromatin condensation nor nuclear fragmentation in any of these situations (see the nuclei of β cells, A–E). Bars = 500 nm (magnification is the same for B and D as well as for C and E).