T cells require TRAIL for optimal graft-versus-tumor activity Journal Article
| Authors: | Schmaltz, C.; Alpdogan, O.; Kappel, B. J.; Muriglan, S. J.; Rotolo, J. A.; Ongchin, J.; Willis, L. M.; Greenberg, A. S.; Eng, J. M.; Crawford, J. M.; Murphy, G. F.; Yagita, H.; Walczak, H.; Peschon, J. J.; van den Brink, M. R. M. |
| Article Title: | T cells require TRAIL for optimal graft-versus-tumor activity |
| Abstract: | 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 tumors1,2. It is expressed on different cells of the immune system and plays a role in natural killer cell-mediated tumor surveillance3-5. In allogeneic hematopoietic-cell transplantation, the reactivity of the donor T cell against malignant cells is essential for the graft-versus-tumor (GVT) effect6. 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 models7,8. 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. |
| Keywords: | controlled study; protein expression; allograft; transplantation, homologous; nonhuman; cell proliferation; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; immune system; fas ligand; apoptosis regulatory proteins; hematopoietic stem cell transplantation; in vivo study; antineoplastic activity; tumor cells, cultured; mice, inbred c57bl; animalia; tumor necrosis factor-alpha; membrane glycoproteins; tumor necrosis factor related apoptosis inducing ligand; hematopoietic cell; natural killer cell; perforin; cytolysis; bone marrow transplantation; graft vs host disease; graft versus leukemia effect; graft vs tumor effect; mice, inbred c3h; tnf-related apoptosis-inducing ligand; priority journal; article |
| Journal Title: | Nature Medicine |
| Volume: | 8 |
| Issue: | 12 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2002-12-01 |
| Start Page: | 1433 |
| End Page: | 1437 |
| Language: | English |
| DOI: | 10.1038/nm797 |
| PUBMED: | 12426560 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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