IFN-γ Level Could Be an Important Indicator to Determine Optimal Timing for Treatment or Prevention of GVHD in NSG Xenogeneic Model

We established xenograft model for graft-versus-host disease (GVHD) using human peripheral blood mononuclear cells (PBMC) in NSG mice. In addition, we also investigated the optimal timing for treatment or prevention of GVHD by observing the changes of inflammatory cytokines in xeno GVHD-induced mice.

We infused various numbers of hPBMCs intravenously into irradiated NOD.scid gamma (NOD.Cg-Prkdc^scidIL2rg^tm1Wjl/SzJ, NSG) mice and assessed the optimal dose of hPBMCs for GVHD model by measuring GVHD clinical score and histopathologic findings as well as inflammatory cytokines.

We observed the compatible findings with GVHD by clinical score as well as immunohistochemical analysis which showed abundant invasion of lymphocytes in the lung, liver, kidney, and small intestines in xeno GVHD-induced mice. On administration of 1 × 10⁶ and 2.5 × 10⁶ hPBMCs, all NSG mice died on 41.6±6.8 days and 24.0±10.4 days, respectively. In contrast, 5 out of 6 NSG mice transplanted with 0.5×10⁶ of hPBMCs survived until 89.6±23.2 days. Additionally, the changes of inflammatory cytokines were analyzed in NSG mice using 1×10⁶ of hPBMC. The concentrations of IFN-γ were markedly increased from day 18 to day 36, however, TNF-α, and IL-2 were rarely detected during 36 days. CD8+ T cells were detected 2–3% in only 1 out of 3 mice and CD 56 was not appeared at all.

These results demonstrated that 2.5×10⁶ of hPBMC was optimal for acute GVHD and 0.5×10⁶ of hPBMCs for chronic GVHD model in NSG mice. In addition, the changes of IFN-γ levels would provide an important evidence for the optimal timing for treatment or prevention of GVHD.

No relevant conflicts of interest to declare.