+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Ligation of OX40 regulates graft-versus-host disease and graft rejection in allogeneic bone marrow transplant recipients



Ligation of OX40 regulates graft-versus-host disease and graft rejection in allogeneic bone marrow transplant recipients



Blood 101(9): 3741-3748



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.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 035221706

Download citation: RISBibTeXText


Related references

Ligation of OX40 (CD134) regulates graft-versus-host disease (GVHD) and graft rejection in allogeneic bone marrow transplant recipients. Blood 101(9): 3741-3748, 2003

Ligation of 4-1BB (CDw137) regulates graft-versus-host disease, graft-versus-leukemia, and graft rejection in allogeneic bone marrow transplant recipients. Journal of Immunology 166(5): 3174-3183, 2001

Tumor immunization of allogeneic bone marrow transplant recipients increases graft versus tumor activity without exacerbating graft versus host disease. Blood 92(10 Suppl. 1 Part 1-2): 438A, 1998

Graft versus tumor activity without graft versus host disease following tumor immunization of allogeneic bone marrow transplant recipients. FASEB Journal 13(4 Part 1): A298, 1999

Immunization of allogeneic bone marrow transplant recipients with tumor cell vaccines enhances graft-versus-tumor activity without exacerbating graft-versus-host disease. Blood 95(7): 2426-2433, 2000

Predicting graft-versus-host disease in allogeneic bone marrow transplant recipients. Transplant Immunology 2(2): 154-155, 1994

Cataract surgery in allogeneic bone marrow transplant recipients with graft-versus-host disease(1). Journal of Cataract and Refractive Surgery 28(3): 417-420, 2002

Cytokine involvement in predicting clinical graft-versus-host disease in allogeneic bone marrow transplant recipients. Bone Marrow Transplantation 13(1): 65-70, 1994

An in vitro predictive test for clinical graft-versus-host disease in allogeneic bone marrow transplant recipients. Bone Marrow Transplantation 5(2): 105-109, 1990

-Rejection of an allogeneic bone marrow graft following successful treatment of severe graft-versus-host disease (GVHD). Japanese Journal of Clinical Hematology 37(2): 134-138, 1996

Impact of Graft Versus Host Disease on Incidence of Secondary Skin Cancers in Allogeneic Bone Marrow Transplant Recipients. Biology of Blood and Marrow Transplantation 24(3): S299-S300, 2018

The oral manifestations of chronic graft-versus-host disease (cGVHD) in paediatric allogeneic bone marrow transplant recipients. Journal of Oral Pathology and Medicine 30(3): 148-153, 2001

Prediction by a modified mixed leukocyte reaction assay of graft-versus-host disease and graft rejection after allogeneic bone marrow transplantation. Transplantation 57(10): 1474-1479, 1994

Epidermal damage in skin of allogeneic bone marrow transplant recipients Relative importance of chemotherapy, conditioning and graft-versus-host disease. Journal of Pathology 168(Suppl. ): 96A, 1992

Graft-versus-leukaemia activity associated with CMV-seropositive donor, post-transplant CMV infection, young donor age and chronic graft-versus-host disease in bone marrow allograft recipients. The Nordic Bone Marrow Transplantation Group. Bone Marrow Transplantation 5(6): 413-418, 1990