In vivo expansion of IL-2 and IL-15 transgenic CTLs. SCID mice engrafted with LCLs were injected with either EBV-CTLs control (ΔCD34v) or EBV-CTLs transgenic for IL-2 (iC.ΔCD34/IL-2v) or IL-15 (iC.ΔCD34/IL-15v) (107 cells). To track their homing and in vivo expansion, CTLs were transduced with the vector encoding eGFP-FFLuc. CTL localization and expansion were monitored using an in vivo imaging system (Xenogen-IVIS Imaging System). Mice did not receive exogenous cytokines after CTL transfer. Panel A shows images of representative mice. The signal intensity measured as photon/sec/cm2/sr (p/s/cm2/sr) was increased in mice receiving CTLs transgenic for IL-2 or IL-15 compared with control cells (ΔCD34v). Panel B illustrates the maximum increase in bioluminescence obtained in 20 mice per group. The expansion of iC.ΔCD34/IL-15v CTLs and iC.ΔCD34/IL-2v CTLs was statistically significant compared with control ΔCD34v (P < .001 and P < .002, respectively). IL-2 and IL-15 transgenic CTLs did not significantly expand in response to allogeneic EBV-LCLs. (C) To evaluate whether the increase in bioluminescence signal corresponded to an increased number of CTLs infiltrating the tumor, mice were euthanized and T-cell infiltration in the bioptic samples was measured using antihuman CD3 staining and FACS analysis (ΔCD34v = 3.8 × 105 p/s/cm2/sr; iC.ΔCD34/IL-2v = 3 × 106 p/s/cm2/sr; iC.ΔCD34/IL-15v = 3.7 × 106 p/s/cm2/sr).
