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IL-10 Exacerbates Xenogeneic GVHD by Inducing Massive Human T Cell Expansion

IL-10 Exacerbates Xenogeneic GVHD by Inducing Massive Human T Cell Expansion

Sojan Abraham, Jang-gi Choi, Chunting Ye, N Manjunath, Premlata Shankar

Clin Immunol. 2015 Jan;156(1):58-64.

PMID: 25463432

Abstract:

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 IL2rγc(null) 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248648	IL-10 human			Price

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