The role of interleukin-12 and interferon-gamma in GVHD and GVL.
The production of interleukin (IL)-12 by antigen-presenting cells after antigen stimulation is a critical step for initiating antigen-specific cellular immune responses, and interferon (IFN)-gamma produced by natural killer cells and activated T cells is a potent mediator of IL-12 effect. However, recent studies have demonstrated that administration of exogenous IL-12 paradoxically inhibits antigen-specific immunity of T cells in vivo, including allogeneic, autoimmune, and viral antigen-initiated T-cell responses. Interestingly, these inhibitory effects are also mediated by IFN-gamma, whose production is induced by IL-12. Thus, IL-12, a potent immunostimulatory cytokine, can paradoxically lead to immunosuppression. Notably, this cytokine has been shown to preserve graft-versus-leukemia (GVL) effects of allogeneic CD8+ T cells while inhibiting graft-versus-host disease (GVHD) in murine allogeneic bone marrow transplantation models. This article will review recent studies concerning the effect of IL-12 and IFN-gamma on the development of GVHD and the induction of GVL effects, and discuss the possible mechanisms responsible for IL-12-mediated separation of GVL effects from the GVHD-promoting activity of allogeneic T cells.
Yang
Y G
YG
Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA. yongguang.yang@tbrc.mgh.harvard.edu
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D006086:Graft vs Host Disease / Q000378:metabolism* / Q000517:prevention & control; D020544:Graft vs Leukemia Effect / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology
D018664:Interleukin-12; D007371:Interferon-gamma