Fig. 1.
(A) Photograph of intact heart from a 22-week-old preterminal DQ8+/+,IAβ-/- female NOD mouse (Right; 0.57 g) compared with that of a healthy age- and sex-matched NOD/LtJ animal (Left; 0.14 g). (B-E) Histology of a typical end-stage diseased heart, stained with hematoxylin and eosin (representative of n = 12 animals). (B) Areas indicated by arrows are shown at higher power in C and D. RA and LV indicate right atrium and left ventricle, respectively. A large organized thrombus (T) fills most of the left atrium. Atrial walls are extremely thin, and the muscle has been replaced with fibrous tissue in most places. Residual patches of dying atrial cardiomyocytes stain bright pink (C) and are associated with mononuclear cell infiltrates. Dense focal mononuclear cell infiltrates associated with myocyte damage can be seen in the ventricular endocardium (D; and at higher magnification in E) and in a perivascular location on the epicardial surface (B, arrowheads). The perivascular mononuclear cells were characterized further by indirect immunofluorescence. The majority of cells showed surface or cytoplasmic IgG expression consistent with B lymphocytes and plasma cells (H; light blue-green staining cells); smaller numbers of CD4+ and CD8+ T cells were also clearly present (I and J, respectively). V, epicardial blood vessel. Note that in H-J all cellular nuclei fluoresce dark blue because of 4′,6-diamidino-2-phenylindole counter-staining, and muscle proteins within the cardiomyocytes fluoresce dark green. F and G show, respectively, pulmonary veins from a normal 5-week-old NOD/LtJ and a 5-week-old DQ8+/+,IAβ-/- animal. (G) A dense collection of mononuclear cells is seen to be associated with the destruction of the ensheathing cardiomyocyte layer on the lower right aspect of the pulmonary vein. Note that during fixation the surrounding lung was less well inflated in G than in F. (Magnifications: B, ×3; C and D and F-J, ×100; E, ×400).