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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2023-2027. Prepublished online as a Blood First Edition Paper on October 5, 2004; DOI 10.1182/blood-2004-08-3036. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-08-3036v1 105/5/2023    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Maeda, Y. Articles by Ferrara, J. L. M. Search for Related Content PubMed PubMed Citation Articles by Maeda, Y. Articles by Ferrara, J. L. M. Related Collections Immunobiology Transfusion Medicine Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Both perforin and Fas ligand are required for the regulation of alloreactive CD8+ T cells during acute graft-versus-host disease Yoshinobu Maeda, Robert B. Levy, Pavan Reddy, Chen Liu, Shawn G. Clouthier, Takanori Teshima, and James L. M. Ferrara From the Departments of Internal Medicine, and Pediatrics, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; the Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL; the Department of Pathology, University of Florida College of Medicine, Gainesville, FL; and the Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan. Fas ligand (FasL) and perforin pathways not only are the major mechanisms of T cell–mediated cytotoxicity but also are involved in homeostatic regulation of these T cells. In the present study, we tested whether CD8+ donor T cells that are deficient in both perforin and FasL (cytotoxic double deficient [cdd]) could induce graft-versus-host disease (GVHD) in a major histocompatibility complex class I–mismatched lethally irradiated murine model. Interestingly, recipients of cdd CD8+ T cells demonstrated significantly greater serum levels of interferon gamma and tumor necrosis factor alpha and histopathologic damage from GVHD than wild-type (wt) T cells on day 30 after allogeneic bone marrow transplantation (P < .05). Wt and either perforin-deficient or FasL-deficient CD8+ T cells expanded early after transplantation followed by a contraction phase in which the majority of expanded CD8+ T cells were eliminated. In contrast, cdd CD8+ T cells exhibited prolonged expansion and reduced apoptosis to alloantigen stimulation in vivo and in vitro. Together these results suggest that donor cdd CD8+ T cells expand continuously and cause lethal GVHD, and that both perforin and FasL are required for the contraction of allo-reactive CD8+ T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Ismail, E. C. Crossley, H. L. Stevenson, and D. H. Walker Relative Importance of T-Cell Subsets in Monocytotropic Ehrlichiosis: a Novel Effector Mechanism Involved in Ehrlichia-Induced Immunopathology in Murine Ehrlichiosis Infect. Immun., September 1, 2007; 75(9): 4608 - 4620. [Abstract] [Full Text] [PDF] J. Yang, S. P. Huck, R. S. McHugh, I. F. Hermans, and F. Ronchese Perforin-dependent elimination of dendritic cells regulates the expansion of antigen-specific CD8+ T cells in vivo PNAS, January 3, 2006; 103(1): 147 - 152. [Abstract] [Full Text] [PDF]

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