@article {542656,
	title = {Ligation of OX40 (CD134) regulates graft-versus-host disease (GVHD) and graft rejection in allogeneic bone marrow transplant recipients.},
	journal = {Blood},
	volume = {101},
	number = {9},
	year = {2003},
	month = {2003 May 1},
	pages = {3741-8},
	abstract = {OX40 (CD134) is expressed on activated T cells; its ligand, OX40 ligand (OX40L) is expressed on dendritic cells, B cells, and activated endothelial cells. To determine how OX40-OX40L interaction affects graft-versus-host disease (GVHD), we used antagonistic anti-OX40L monoclonal antibody (mAb) or OX40(-/-) donor or OX40L(-/-) recipient mice. Similar degrees of GVHD reduction were observed with each approach. Despite the fact that OX40 is up-regulated on both CD4(+) and CD8(+) T cells isolated during GVHD, the major effects of OX40 ligation were on CD4(+) and not CD8(+) T-cell-mediated alloresponses as assessed in both GVHD and engraftment model systems. GVHD inhibition by blockade of the OX40/OX40L pathway did not require CD28 signaling. Some studies have indicated OX40 is essential for inducing T-helper type 2 (Th2) responses. However, in vivo blockade of OX40-OX40L interactions reduced GVHD mortality induced by either signal transducer and activator of transcription-6(-/-) (Stat-6(-/-)) (Th2-defective) or Stat-4(-/-) (Th1-defective) major histocompatibility complex (MHC)-disparate splenocytes, indicating that the GVHD-ameliorating effects did not require Stat-4 or Stat-6 signaling. Although OX40L has been reported to be expressed on activated T cells, no effects on GVHD were observed when OX40L(-/-) versus OX40L(+/+) T cells were infused in different models. These data provide insights as to the mechanisms responsible for OX40/OX40L regulation of GVHD.},
	keywords = {Animals, Antibodies, Monoclonal, Antibody Specificity, Antigens, CD27, Antigens, CD28, Bone Marrow Transplantation, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Crosses, Genetic, Dendritic Cells, DNA-Binding Proteins, Graft Rejection, Graft vs Host Disease, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, SCID, Radiation Chimera, Receptors, OX40, Receptors, Tumor Necrosis Factor, Signal Transduction, Specific Pathogen-Free Organisms, STAT4 Transcription Factor, STAT6 Transcription Factor, Th1 Cells, Th2 Cells, Trans-Activators, Transplantation, Homologous, Tumor Necrosis Factors},
	issn = {0006-4971},
	doi = {10.1182/blood-2002-10-3048},
	author = {Blazar, Bruce R and Sharpe, Arlene H and Chen, Andy I and Panoskaltsis-Mortari, Angela and Lees, Christopher and Akiba, Hisaya and Yagita, Hideo and Killeen, Nigel and Taylor, Patricia A}
}
