Abstract
Previous studies have demonstrated that infusion of allogeneic matched and haploidentical peripheral blood stem cells with minimal conditioning (microtransplantation) achieved durable responses in patients with refractory leukemia/lymphoma in the absence of engraftment. The mechanisms underlying this response have not been thoroughly elucidated, while host-versus-graft reactions are likely to have an important role. The present study established a mismatched microtransplantation mouse model of leukemia to study the roles of CD4+ T cells and CD8+ T cells in changes of interferon (IFN)-γ and interleukin (IL)-4 release to explore the mechanisms of the effects of microtransplantation. It was demonstrated that IFN-γ is critical to the antileukemia response in a mouse model of microtransplantation. The therapeutic efficacy was associated with the number of CD4+ T cells (Pearson's r=0.722). In addition, CD8+ T cells increased the release of IFN-γ with assistance from CD4+ T cells. IL-2 augmented IFN-γ release, partly by increasing CD4+ T cells (42.8 vs. 35.6%; P<0.05). The present study suggested that the release of IFN-γ via cooperation of CD4+ T cells and CD8+ T cells represents a crucial mechanism in the antileukemia responses of recipient leukemic mice treated by microtransplantation. During this process, the cooperation of CD4+ T cells and CD8+ T cells was demonstrated to have a major role in the antileukemia effect. IL-2 may be developed into an agent used for improving the efficacy of microtransplantation by increasing CD4+ T cells.