Function of VAV1 mutations in physiological differentiation of splenic T cells. (A) Schematic showing structures of VAV1-mutant proteins resulting from nonsynonymous mutations, in-frame deletions, and fusion with various partners identified in PTCL-NOS,^3-5  AITL,⁷  ALCL,³  and ATL.²  (B) Cell fractions of splenocytes harvested from mice indicated genotypes at 12 weeks of age before tumor development. (i) Percentages of naive T cells defined by CD4⁺CD62L⁺CD44⁻ and those of memory T cells defined by CD4⁺CD62L⁻CD44⁺. (ii) Percentage of CD4⁺PD-1⁺ICOS⁺ cells. The number of mice analyzed is as follows: WT, n = 6; VAV1-Tg, n = 9; p53^−/−, n = 10; p53^−/−VAV1-Tg, n = 9. *P < .05. (C) Representative flow cytometric data indicating CD4 naive and memory T cells (i) and CD4⁺PD-1⁺ICOS⁺ cells (ii) in indicated genotypes at 12 weeks of age. (D) Phosphorylated VAV1 (pVav1) protein expression examined by flow cytometry in naive T cells sorted from splenocytes of V-Fus or WT mice with or without TCR stimulation. Black line indicates WT; red line, V-Fus expression data. Dotted line indicates nonstimulated status; solid line, stimulated status.