Brief CommunicationIL-10 exacerbates xenogeneic GVHD by inducing massive human T cell expansion

- Human IL-10 has a direct pathogenic role in graft versus host disease.
- IL-10 exacerbates GVHD by inducing massive expansion of T cells.
- The pathogenic effects of IL-10 can be reversed in vivo by IL-10R blockade.
- Blockade of IL-10 signaling may provide a therapeutic option to treat GVHD.

Although patients with GVHD have elevated serum levels of IL10, whether its role is protective or pathogenic remains unclear. Here, we used a humanized mouse model to study the role of IL-10 in GVHD. When human PBMCs were engrafted in NOD-scid IL2rγcnull mice expressing human IL-10, the T cells underwent massive expansion resulting in lethality by day 21, whereas control mice survived for at least 40 days. Histopathology of the liver showed extensive mononuclear cell infiltration in IL-10 expressing but not in control mice. Corresponding to their aggressiveness, the T cells in the IL-10 group exhibited predominantly an effector memory phenotype (CD45RO+CD27−) while in control mice, the T cells were of transitional memory phenotype (CD45RO+CD27+). Further, IL-10 receptor blocking antibody was able to protect the animals from GVHD. Since our results demonstrate a direct pathogenic role for IL-10, blockade of IL-10 signaling may provide a therapeutic option for GVHD.