T cells require TRAIL for optimal graft-versus-tumor activity

Nat Med. 2002 Dec;8(12):1433-7. doi: 10.1038/nm1202-797. Epub 2002 Nov 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Graft vs Host Disease / etiology
  • Graft vs Tumor Effect / immunology*
  • Hematopoietic Stem Cell Transplantation
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • T-Lymphocytes / immunology*
  • TNF-Related Apoptosis-Inducing Ligand
  • Transplantation, Homologous
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / physiology*


  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • TNF-Related Apoptosis-Inducing Ligand
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha