Fig 1.
Histopathology in isogenic and allogenic kidney grafts.
PAS stainings illustrating histopathology of mouse isografts (A, B) and allografts (C-F). Isografts showed almost normal renal morphology with some focal interstitial inflammatory infiltrates (A and B). Mouse allografts revealed severe rejection (C and D). In addition, allografts with arterial endothelialitis (Banff IIA, E) and transmural arteriitis (Banff III, F) are shown. Bars represent 20 μm in A and B, 50 μm in B and D and 100 μm in E and F.
Fig 2.
Characterization of infiltrating leukocyte subtypes.
Immunohistochemistry with staining for CD3-positive cells showed mild baseline CD3-positive T-lymphocyte expression isogenic kidney grafts. Allogenic kidney grafts had dense infiltrates of CD3-positive lymphocytes (red) at day 7 after transplantation (magnificatin 200-fold). The tubular autofluorescence is overlaid in green for anatomical orientation. Flow cytometric analysis confirmed that in allogenic ktx βTCR-positive (TCR+) cells were the most abundant leukocyte subset, while in isogenic ktx slightly enhanced TCR+ cell infiltration was present (gating examples among live, CD11b+ cells). More details on the cell sorting process are provided in S1 Fig. *p<0.05, ## p<0.01 and ### p<0.001 in comparison to allogenic group.
Fig 3.
Inflammation and cell infiltration in isogenic and allogenic kidney grafts measured by DWI and histology.
Representative ADC maps of a control kidney (A, first column) and isogenic (second column) and allogenic kidney grafts (third column) at day 1 (B) and day 6 (C) are shown after adjustment for multiple comparisons. Mean ADC values in cortex and outer medulla as well as significant group differences are indicated. Corresponding to ADC reduction in allogenic kidney grafts histology revealed elevated tubulo-interstitial inflammation. This correlated with enhanced DAPI positive nuclei visualized in blue (D). Representative DAPI stains, overlaid with tubular autofluorescence for anatomical orientation, of an isograft (second column) and an allograft (third column) are shown. Inflammation was scored semi-quantitatively in PAS stained sections (magnificatin 200 fold). *p<0.05, **p<0.01, ## p<0.01 and ### p<0.001 compared to allogenic kidney grafts.
Table 1.
Functional MRI parameters after isogenic and allogenic ktx and in control animals.
Fig 4.
Inflammation and tissue edema in isogenic and allogenic kidney grafts measured by T2-mapping and histology.
T2 maps of a control kidney (A, first column) and isogenic (second column) and allogenic kidney grafts (third column) at day 1 (B) and day 6 (C) are shown. Differentiation of renal compartments such as cortex (C), outer (OSOM) and inner stripe of the outer medulla (ISOM) is visualized in panel A. Note the loss of T2-difference between cortex and ISOM in allogenic grafts at d6 after ktx. This corresponds with the loss of tubular autofluorescence (green), which was associated with rejection and loss of tubular function in allogenic ktx (D). PAS stain shows severe endothelialitis and concomitant surrounding edema in allogenic graft (D). Bar represents 50 μm. *p<0.05, **p<0.01, ***p<0.001, ### p<0.001 compared to allogenic kidney grafts.
Fig 5.
Diagnostic accuracy of functional MRI parameters to discriminate allografts with acute rejection from isografts without rejection.
ROC curve analysis shows diagnostic accuracies of ADC values (A) and T2 relaxation times (B) to discriminate allografts with acute rejection from isografts without rejection. Area under the curve, Youden selected thresholds as well as sensitivities and specificities are given in Table 2.
Table 2.
Diagnostic accuracy of functional MRI parameters to discriminate allografts with acute rejection from isografts without rejection.