{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T21:40:54Z","timestamp":1772574054511,"version":"3.50.1"},"reference-count":35,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fas ligand (FasL) and perforin pathways not only are the major mechanisms of T cell\u2013mediated 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\u2013mismatched 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 &amp;lt; .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.<\/jats:p>","DOI":"10.1182\/blood-2004-08-3036","type":"journal-article","created":{"date-parts":[[2004,10,6]],"date-time":"2004-10-06T01:33:27Z","timestamp":1097026407000},"page":"2023-2027","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":53,"title":["Both perforin and Fas ligand are required for the regulation of alloreactive CD8+ T cells during acute graft-versus-host disease"],"prefix":"10.1182","volume":"105","author":[{"given":"Yoshinobu","family":"Maeda","sequence":"first","affiliation":[{"name":"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."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert B.","family":"Levy","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavan","family":"Reddy","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn G.","family":"Clouthier","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanori","family":"Teshima","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James L. M.","family":"Ferrara","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021222363455700_REF1","doi-asserted-by":"crossref","unstructured":"Shlomchik WD, Couzens MS, Tang CB, et al. Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science.1999;285: 412-415.","DOI":"10.1126\/science.285.5426.412"},{"key":"2020021222363455700_","doi-asserted-by":"crossref","unstructured":"Zhang Y, Louboutin JP, Zhu J, Rivera AJ, Emerson SG. 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