Coinfusion of human conventional Tcons and Tregs exerts a GVL effect without GVHD in mice with human leukemia. (A) NSG mice were given 3.5 Gy TBI and then infused with 7 × 106 primary human AML cells. Thirty days after leukemia engraftment, mice were treated with 3 × 106 Tcons and/or 3 × 106 Tregs. Untreated (○) or Treg-infused (▲) mice died of leukemia; Tcon-treated mice (●) died of GVHD; mice coinfused with 3 × 106 Tcons and 3 × 106 Tregs (▪) survived without GVHD. (B) Human T cells harvested from bone marrow of mice treated with the Tcon plus Treg combination exerted allogeneic lysis against leukemia (black bar) and PHA blasts (white bar) autologous to leukemia to an effector to target ratio = 5:1 in a chromium-releasing cytotoxicity assay. (C) Mice infused with 2 × 106 Ph+ cell line cells (SUP-B15) and treated with 3 × 106 Tcons and 3 × 106 Tregs (▪) survived leukemia without GVHD. Untreated mice and those infused with 3 × 106 Tregs (▲) died of leukemia within 60 days; mice infused with 3 × 106 Tcons (●) died of GVHD. (D) Similar outcomes were obtained with Burkitt’s cell line (Namalwa). All experiments were conducted in duplicate in groups of 5 mice.
