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.

Publication Type:

Journal Article

Source:

Journal of immunology (Baltimore, Md. : 1950), Volume 188, Issue 2, p.724-34 (2012)

Keywords:

* Cell Movement, 2012, Animals, Antigens, CD274, CD8-Positive T-Lymphocytes, Cell Proliferation, Center-Authored Paper, Clinical Research Division, Consortium Authored Paper, Graft Survival, Graft vs Host Disease, Hepatocytes, January 2012, Liver Transplantation, Lymphocyte Activation, MICE, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Transplantation Tolerance, Up-Regulation

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.