ITK-SYK^CD19-Cre mice develop clonal PTCLs. (A) ITK-SYK^CD19-Cre mice succumb to disease. Kaplan-Meier curve of ITK-SYK^CD19-Cre (n = 18) and control (CD19-Cre) mice (n = 10). (B) Splenomegaly in ITK-SYK^CD19-Cre mice. Representative spleens from 50-wk-old control and ITK-SYK^CD19-Cre mice are shown (in centimeters). (C) Solid organ infiltration with abnormally proliferating T cells in ITK-SYK^CD19-Cre mice. H&E staining and immunohistochemistry with anti-CD3 and anti–Ki-67 antibodies were performed on liver (LIV) and lung (LNG) sections. Bars, 1 mm. Data representative of six diseased ITK-SYK^CD19-Cre mice are shown. (D) Bone marrow (BM) or spleen (SPL) cell suspensions of 50-wk-old control and ITK-SYK^CD19-Cre mice were stained against TCR-β. The frequency of eGFP⁺ T cells in a representative ITK-SYK^CD19-Cre mouse is indicated. (E) Expanded T cells in ITK-SYK^CD19-Cre mice display an activated phenotype. CD44 and CD62L surface expression on affected T cells or controls was assessed using FACS. One representative example of CD4⁺ T cells is shown. (F) Spleen cells from diseased ITK-SYK^CD19-Cre mice (n = 16) were stained against CD4 and CD8. Examples of preferential CD4⁺ T cell (Type I) or CD8⁺ T cell (Type II) expansions are shown. (G) T cell populations in ITK-SYK^CD19-Cre mice are clonal. Single cell suspensions from spleens of individual mice were stained with antibodies against CD4, CD8, and a panel of antibodies against TCR-Vβ chains (see Materials and methods). Frequencies of CD4⁺ or CD8⁺ cells expressing the indicated TCR-Vβ chains in control (open histograms) or diseased ITK-SYK^CD19-Cre (gray histograms) mice are shown. Data in B and D–G are representative of six independent experiments with a total number of at least 10 mice analyzed per genotype are shown. If not indicated otherwise, all panels show data from ITK-SYK^CD19-Cre mice that were older than 40 wk and showed disease symptoms.