Figure 1
Allogeneic recipients of MyD88KO donor TCD-BM exhibit severe GVHD morbidity and mortality with intestinal damage. Lethally irradiated F1 recipients were given 5 × 106 WT or MyD88KO TCD-BM cells plus 1 × 106 purified WT T cells from allogeneic B6 donors (n=10 in each group, allo WT and allo KO). B6 animals were irradiated and transplanted with 5 × 106 WT or MyD88KO TCD-BM cells plus 1 × 106 purified WT T cells from syngeneic B6 donors (n=5 in each group, syn WT and syn KO). Control mice were given only TCD-BM from WT or MyD88KO mice (thus without co-transplantation of B6 T cells; n=10 in each group, allo WT TCD-BM and allo KO TCD-BM), or were not given TCD-BM (total body irradiation (TBI), n=5) after the irradiation. (a) Kaplan–Meier survival curve of the transplanted mice. Percent survival after transplantation, allo WT vs. allo KO by the Wilcoxon rank-sum test. (b) Corresponding GVHD scores (left) and weight loss (right). Animals were assessed weekly for weight loss and clinical severity, allo WT vs. allo KO by the Mann-Whitney U-test. Data are presented as means±s.e.m. and are representative of duplicate experiments. (c) Whole gut was isolated from non-GVHD controls without T cells (allo WT TCD-BM and allo KO TCD-BM) and allogeneic recipients (allo WT and allo KO) on day 5. The severity of gut damage was grossly compared and representative animals are shown. The lengths of the small intestines (SI) are presented as means±s.e.m. (d) The extent of epithelial injury of the SI was evaluated. Areas of grade ⩾3 were classified as severely affected (arrows), and the proportions of such severe SI lesions were compared among different groups of transplantation. Representative pathological findings in severe lesions are indicated by arrows. The mid-panel figures (× 12.5) are the areas within the black squares of the left figures and the right figures (× 200) are representative of the severe lesions. The extent of pathological damage to SI was evaluated using the semi-quantitative scoring system described in Methods section, in all the transplantation groups (n=5 in each group). Lengths of the lesions (⩾ grade 3) were plotted as percentages of the entire SI lengths,39 and the values were denoted as pathological scores and compared among the different groups. Data are presented as means±s.e.m. Data shown in c andd are representative of two independent experiments. BMT, bone marrow transplantation; GVHD, graft-vs.-host disease; KO, knockout; TCD-BM, T-cell depleted bone marrow; WT, wild type.
