title: Loss of B7-H1 expression by recipient parenchymal cells leads to expansion of infiltrating donor CD8+ T cells and persistence of graft-versus-host disease.
abstract: Previous experimental studies have shown that acute graft-versus-host disease (GVHD) is associated with two waves of donor CD8(+) T cell expansion. In the current studies, we used in vivo bioluminescent imaging, in vivo BrdU labeling, and three different experimental GVHD systems to show that B7-H1 expression by recipient parenchymal cells controls the second wave of alloreactive donor CD8(+) T cell expansion and the associated second phase of GVHD. Loss of B7-H1 expression by parenchymal cells during the course of GVHD was associated with persistent proliferation of donor CD8(+) T cells in GVHD target tissues and continued tissue injury, whereas persistent expression of B7-H1 expression by parenchymal cells led to reduced proliferation of donor CD8(+) T cells in GVHD target tissues and resolution of GVHD. These studies demonstrate that parenchymal cell expression of B7-H1 is required for tolerizing infiltrating T cells and preventing the persistence of GVHD. Our results suggest that therapies designed to preserve or restore expression of B7-H1 expression by parenchymal tissues in the recipient could prevent or ameliorate GVHD in humans.
authors.affiliation: Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Li
authors.forename: Ruishu
authors.initials: R
authors.lastname: Deng
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Can
authors.initials: C
authors.lastname: Liu
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.forename: James
authors.initials: J
authors.lastname: Young
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Meng
authors.forename: Chantal
authors.initials: C
authors.lastname: Du
authors.forename: Wendong
authors.initials: W
authors.lastname: Huang
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Yuanzhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
authors.forename: Defu
authors.initials: D
authors.lastname: Zeng
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D022781:Hepatocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology / Q000379:methods / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023001:Transplantation Tolerance / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse