Dichotomous Role of Interferon-γ in Allogeneic Bone Marrow Transplant

IFN-γ-producing cells show different effects on GVHD and GVL.

⊕ increase; ⊖ inhibit; unknown.

Role of IFN-γ during the development of GVHD and GVL. The conditioning regimen leads to damage of host tissues and allows the translocation of LPS and other pro-inflammatory cytokines into the circulation, leading to the activation of donor T cells by host APC [17]. Interaction between donor IL-12-producing APC with donor T cells can increase the IFN-γ production by activated T cells. High local levels of IFN-γ subsequently induce IDO expression on donor APC (Lu et al., 2009, in preparation). IDO⁺ APCs help maintain the tolerant phenotype of T-reg, which inhibits the Th1 and Th17 polarization of donor T cells, resulting in downmodulation of T cell alloreactivity and GVHD effect [83].

IFN-γ-induced IDO expression on host epithelial cells inhibits GVHD. Donor T cells induce GVHD effects that cause target epithelial cell apoptosis . IDO expression on host epithelial cells induced by IFN-γ from donor T cells inhibits GVHD [85]. In addition, IFN-γ enhances GVL effect through both direct and indirect mechanisms, resulting in apoptosis of tumor cells [18].