Expression of the T-cell activation antigen, OX-40, identifies alloreactive T cells in acute graft-versus-host disease.

Abstract

The OX-40 molecule is expressed on the surface of recently activated T lymphocytes. The presence of OX-40 on CD4+ T cells was analyzed in a rat haplo-identical (parental --> F1) bone marrow transplant model of acute graft-versus-host disease (aGVHD). Increased numbers of activated CD4+ T cells that expressed the OX-40 antigen were detected in peripheral blood soon after transplantation before the earliest sign of disease. The peak of OX-40 expression occurred 12 days posttransplantation with a range of 18% to 36% of circulating T cells and remained 10-fold above background, never returning to baseline. A slight increase in OX-40 expression (range, 1% to 6%) was also detected on peripheral blood lymphocytes from control syngeneic F1 --> F1 recipients. OX-40+ T cells were isolated from spleen, skin, lymph node, and liver tissue of rats undergoing aGVHD, but not in syngeneic transplants. OX-40+ T cells isolated from these tissues were of donor origin and were shown to be alloreactive. These data raise the possibility of using the OX-40 antibody to detect and deplete selectively the T cells that cause aGVHD.

• Authors: T V Tittle, A D Weinberg, C N Steinkeler, R T Maziarz
• Journal: Blood (Blood) Vol. 89 Issue 12 Pg. 4652-8 (Jun 15 1997) ISSN: 0006-4971 [Print] United States
• PMID: 9192792 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Biomarkers
• Receptors, OX40
• Receptors, Tumor Necrosis Factor
• Tnfrsf4 protein, rat
• Tumor Necrosis Factor Receptor Superfamily, Member 7

Topics

• Animals
• Biomarkers
• Bone Marrow Transplantation (adverse effects, immunology)
• CD4-Positive T-Lymphocytes (immunology, transplantation)
• Cell Separation
• Female
• Graft vs Host Disease (etiology, immunology)
• Lymphocyte Activation
• Lymphocyte Depletion (methods)
• Radiation Chimera
• Rats
• Rats, Inbred BUF
• Rats, Inbred Lew
• Receptors, OX40
• Receptors, Tumor Necrosis Factor
• T-Lymphocyte Subsets (immunology, transplantation)
• Transplantation, Homologous (adverse effects, immunology)
• Tumor Necrosis Factor Receptor Superfamily, Member 7 (biosynthesis, genetics)
• Up-Regulation