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

Xiaofan Li, Ruishu Deng, Wei He, Can Liu, Miao Wang, James Young, Zhipeng Meng, Chantal Du, Wendong Huang, Lieping Chen, Yuanzhong Chen, Paul Martin, Stephen Forman, Defu Zeng

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)724-734
Number of pages11
JournalJournal of Immunology
Volume188
Issue number2
DOIs
StatePublished - Jan 15 2012
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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