T cells require TRAIL for optimal graft-versus-tumor activity
| Autor: | Jennifer Ongchin, Andrew S. Greenberg, George F. Murphy, Cornelius Schmaltz, Jacques J. Peschon, Marcel R.M. van den Brink, Onder Alpdogan, Jimmy A. Rotolo, James M. Crawford, Barry J. Kappel, Henning Walczak, Jeffrey M. Eng, Lucy M. Willis, Hideo Yagita, Stephanie J. Muriglan |
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| Rok vydání: | 2002 |
| Předmět: |
T-Lymphocytes
medicine.medical_treatment T cell Graft vs Host Disease Hematopoietic stem cell transplantation Biology General Biochemistry Genetics and Molecular Biology TNF-Related Apoptosis-Inducing Ligand Mice Interleukin 21 Immune system Tumor Cells Cultured medicine Animals Transplantation Homologous Cytotoxic T cell Mice Inbred C3H Membrane Glycoproteins Tumor Necrosis Factor-alpha ZAP70 Graft vs Tumor Effect Hematopoietic Stem Cell Transplantation General Medicine Natural killer T cell Mice Inbred C57BL Transplantation medicine.anatomical_structure Immunology Apoptosis Regulatory Proteins |
| Zdroj: | Nature Medicine. 8:1433-1437 |
| ISSN: | 1078-8956 |
| DOI: | 10.1038/nm797 |
| Popis: | Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that exhibits specific tumoricidal activity against a variety of tumors. It is expressed on different cells of the immune system and plays a role in natural killer cell-mediated tumor surveillance. In allogeneic hematopoietic-cell transplantation, the reactivity of the donor T cell against malignant cells is essential for the graft-versus-tumor (GVT) effect. Cytolytic activity of T cells is primarily mediated through the Fas-Fas ligand and perforin-granzyme pathways. However, T cells deficient for both Fas ligand and perforin can still exert GVT activity in vivo in mouse models. To uncover a potential role for TRAIL in donor T cell-mediated GVT activity, we compared donor T cells from TRAIL-deficient and wild-type mice in clinically relevant mouse bone-marrow transplantation models. We found that alloreactive T cells can express TRAIL, but the absence of TRAIL had no effect on their proliferative and cytokine response to alloantigens. TRAIL-deficient T cells showed significantly lower GVT activity than did TRAIL-expressing T cells, but no important differences in graft-versus-host disease, a major complication of allogeneic hematopoietic cell transplantation, were observed. These data suggest that strategies to enhance TRAIL-mediated GVT activity could decrease relapse rates of malignancies after hematopoietic cell transplantation without exacerbation of graft-versus-host disease. |
| Databáze: | OpenAIRE |
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