FIGURE 3.
LAT ablation in peripheral T cells results in a LATY136F-like lymphoproliferative syndrome. 2 × 107 splenocytes from untreated ERCre+LATf/− littermates were adoptively transferred to syngeneic LAT−/− recipients; LATf/− splenocytes were used as controls. Five weeks later, the recipients were treated with tamoxifen on 2 consecutive days. Tamoxifen treatment was then repeated once a week for 4–5 weeks. Data are representative of two independent experiments with three mice per genotype in each experiment. A, enlarged spleens from mice that received ERCre+LATf/− cells. B, total numbers of CD4+, CD8+, and CD4+Foxp3+ cells in spleens (top panel) and expression of CD4 versus CD8 in spleens (bottom panel). A two-tailed Student's t test analysis was performed; * represents p < 0.05. C, expression of GFP versus TCRβ in spleens, gated on CD4+ cells. D, cytokine production. Splenocytes from both groups of recipients were either left untreated or stimulated with PMA plus ionomycin for 5 h. Intracellular staining of IL-4 in CD4+-gated splenocytes is shown. The numbers on the FACS plots represent the percentages of the gated populations. E, the IgM versus IgD profile of B220+-gated splenocytes. F, percentage of Foxp3+ cells in CD4+ splenocytes (top panel). Foxp3 versus GFP expression in CD4+ splenocytes (bottom panel). G, CTLA-4 (top panel) and CD25 (bottom panel) versus GFP in CD4+Foxp3+ splenocytes.