title: IL-10 exacerbates xenogeneic GVHD by inducing massive human T cell expansion.
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.
authors.affiliation: Department of Biomedical Sciences, Center of Excellence in Infectious Disease, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Sojan
authors.initials: S
authors.lastname: Abraham
authors.affiliation: Department of Biomedical Sciences, Center of Excellence in Infectious Disease, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Jang-gi
authors.initials: JG
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, Center of Excellence in Infectious Disease, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Chunting
authors.initials: C
authors.lastname: Ye
authors.affiliation: Department of Biomedical Sciences, Center of Excellence in Infectious Disease, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: N
authors.initials: N
authors.lastname: Manjunath
authors.affiliation: Department of Biomedical Sciences, Center of Excellence in Infectious Disease, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA. Electronic address: Premlata.shankar@ttuhsc.edu.
authors.forename: Premlata
authors.initials: P
authors.lastname: Shankar
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000503:physiopathology*; D064593:Heterografts; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D023421:Models, Animal; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D016753:Interleukin-10
keywords: GVHD;; IL-10:; NSG mice; PBMCs;