Figure 1.
IL-7Rα expression results in progressive thymic hyperplasia and disseminated, fatal T-cell leukemia/lymphoma. (A) Thymus cellularity vs age from wild-type F5 control and F5 TetIL-7RON mice. Numbers indicate slope of line fit and 95% confidence intervals. (B) CD4 vs CD8 expression by thymocytes and splenocytes from TetIL-7RON mice (n = 36). Lymphoma/leukemia present in thymus and spleen, characterized by their expression of CD4 and CD8 into DN, CD8 SP, DP, and CD4 SP. A representative example of each phenotype is shown and the percent incidence of phenotype indicated under the phenotypic label. (C) CD4 vs CD8 expression by thymocytes and splenocytes from TetIL-7RON or control C57Bl6/J mice. Histograms are of Ki67 labeling of thymocytes (top) and splenocytes (bottom) of the indicated subpopulation from either TetIL-7RON or C57Bl6/J control mice. (D) Survival of cohorts of TetIL-7RON (n = 8) vs TetIL-7ROFF (n = 4) and TreIL-7R+ rtTA– Il7r−/− mice (n = 4). Mice were culled when they reached the defined humane end point (see “Methods”). P = .0003. (E) Phenotype in the indicated organs of F5 TetIL-7RON mice identified with clinical signs of disease (tumor), as compared with IL-7RWT F5 control mice (control). Density plots are of CD4 vs CD8 in the thymus, spleen and bone marrow of the indicated conditions. (F) Malignant thymocytes from donor mouse in (E) were transferred into Rag1−/− recipients (n = 8). Four weeks later, thymus, spleen, and bone marrow were analyzed for the presence of donor cells. Shown is pooled data of 2 (D) or 6 (A-B) independent experiments or mean results of 3 (C,E-F) independent experiments.