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Related Collections Immunobiology Transplantation Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2001, Vol. 97, No. 9, pp. 2886-2895 TRANSPLANTATION Differential use of Fas ligand and perforin cytotoxic pathways by donor T cells in graft-versus-host disease and graft-versus-leukemia effect Cornelius Schmaltz, Onder Alpdogan, Kirsten J. Horndasch, Stephanie J. Muriglan, Barry J. Kappel, Takanori Teshima, James L. M. Ferrara, Steven J. Burakoff, and Marcel R. M. van den Brink From the Departments of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; the Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA; and the Departments of Internal Medicine and Pediatrics, University of Michigan, Ann Arbor, MI. In allogeneic bone marrow transplantation (BMT) donor T cells are primarily responsible for antihost activity, resulting in graft-versus-host disease (GVHD), and for antileukemia activity, resulting in the graft-versus-leukemia (GVL) effect. The relative contributions of the Fas ligand (FasL) and perforin cytotoxic pathways in GVHD and GVL activity were studied by using FasL-defective or perforin-deficient donor T cells in murine parent  F1 models for allogeneic bone marrow transplantation. It was found that FasL-defective B6.gld donor T cells display diminished GVHD activity but have intact GVL activity. In contrast, perforin-deficient B6.pfp/ donor T cells have intact GVHD activity but display diminished GVL activity. Splenic T cells from recipients of B6.gld or B6.pfp/ T cells had identical proliferative and cytokine responses to host antigens; however, splenic T cells from recipients of B6.pfp/ T cells had no cytolytic activity against leukemia cells in a cytotoxicity assay. In experiments with selected CD4+ or CD8+ donor T cells, the FasL pathway was important for GVHD activity by both CD4+ and CD8+ T cells, whereas the perforin pathway was required for CD8-mediated GVL activity. These data demonstrate in a murine model for allogeneic bone marrow transplantation that donor T cells mediate GVHD activity primarily through the FasL effector pathway and GVL activity through the perforin pathway. This suggests that donor T cells make differential use of cytolytic pathways and that the specific blockade of one cytotoxic pathway may be used to prevent GVHD without interfering with GVL activity. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Sun, M. Li, T. J. Sayers, L. A. Welniak, and W. J. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020