Cooperation of CD4+ T cells and CD8+ T cells and release of IFN-γ are critical for antileukemia responses of recipient mice treated by microtransplantation.

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.