Human IL-10 exacerbates graft versus host disease in NOD-scid IL2rγcnull mice transplanted with human PBMCs (TRAN3P.910)

Dysregulated cytokine production plays an important role in the clinical manifestation of acute graft-versus-host disease (aGVHD) following allogeneic bone marrow transplantation (BMT). The role of IL-10, anti-inflammatory cytokine in GVHD pathogenesis remains ambiguous. There are reports showing both beneficial and adverse effects of this cytokine in GVHD progression. Hence to determine the role of IL-10 in GVHD progression, we expressed hIL-10 in NOD-scid IL2rγcnull mice (NSG) by hydrodynamic gene delivery and evaluated its effect on xeogenic GVHD manifestations. We demonstrate that hIL-10 is capable of accelerating the hPBMC induced xeno-GVHD in NSG mice. The marked human T cell infiltration and tissue destruction observed in presence of IL-10 suggest that human IL-10 potently activates and expands pathogenic human T cells with the capacity to induce xeno GVHD. The significant reduction in the number of human cells at the initial phase and robust expansion at later stage suggests that those escapes IL-10 mediated suppression is responsible for the development of xeno-GVHD. Taken together, our results demonstrate for the first time that xenografted human T cells expand in response to IL-10 and mediate tissue damage in xeno GVHD mouse model. These finding provide caution against using rhIL-10 as an immunosuppressive cytokine after allogenic BMT.