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rdf:type |
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lifeskim:mentions |
umls-concept:C0039194,
umls-concept:C0070410,
umls-concept:C0085358,
umls-concept:C0253023,
umls-concept:C0851285,
umls-concept:C0856825,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1706438,
umls-concept:C2698600
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pubmed:issue |
5
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pubmed:dateCreated |
2005-2-17
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2023-7
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15466930-Acute Disease,
pubmed-meshheading:15466930-Animals,
pubmed-meshheading:15466930-Bone Marrow Transplantation,
pubmed-meshheading:15466930-CD8-Positive T-Lymphocytes,
pubmed-meshheading:15466930-Cell Culture Techniques,
pubmed-meshheading:15466930-Fas Ligand Protein,
pubmed-meshheading:15466930-Graft vs Host Disease,
pubmed-meshheading:15466930-Histocompatibility,
pubmed-meshheading:15466930-Histocompatibility Antigens Class I,
pubmed-meshheading:15466930-Lymphocyte Transfusion,
pubmed-meshheading:15466930-Membrane Glycoproteins,
pubmed-meshheading:15466930-Mice,
pubmed-meshheading:15466930-Mice, Inbred Strains,
pubmed-meshheading:15466930-Models, Animal,
pubmed-meshheading:15466930-Perforin,
pubmed-meshheading:15466930-Pore Forming Cytotoxic Proteins,
pubmed-meshheading:15466930-Transplantation, Homologous
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pubmed:year |
2005
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pubmed:articleTitle |
Both perforin and Fas ligand are required for the regulation of alloreactive CD8+ T cells during acute graft-versus-host disease.
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pubmed:affiliation |
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, 1500 East Medical Center Dr, Ann Arbor, MI 48109-0942, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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