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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1993-7-14
pubmed:abstractText
Surprisingly little graft-versus-host disease (GVHD) has been observed in severe combined immunodeficient (SCID) mice injected intraperitoneally (IP) with human blood lymphocytes (hu-PBL-SCID), which raised the question as to whether GVHD in such a distant species is sporadic or suppressed because of immunologic reasons. After screening for blood T-cell chimerism, we hereby describe generalized lethal xenogeneic human GVHD in unconditioned SCID chimeras, which resembles GVHD in SCID mice injected with allogeneic lymphocytes. We adapted an immunocytochemical slide method for minute cell numbers, which allowed us to follow, by multimarker phenotyping of weekly mouse-tail bleeds, the chimeric status of 100 hu-PBL-SCID injected with 10(7) or 10(8) hu-PBL of Epstein-Barr virus- (EBV-) donors. More than half of the mice showed no or less than 2% T cells. However, 13% to 21% developed substantial blood T-lymphocyte chimerism (10% to 80% human CD+ cells) and high mortality. Immunohistology showed more human CD8+ than CD4+ T cells in the splenic white pulp. The cells developed HLA-DR activation markers and infiltrated the red pulp where human B cells also appeared. Expression of activation and proliferation markers increased within 5 to 6 weeks. Many human CD3+ cells were also found in the portal triads of the liver and in the lung, pancreas, and kidney. The thymus also became heavily infiltrated. The intestines and skin of hu-PBL-SCID were less infiltrated by donor cells than in SCID with allogeneic GVHD. The tongue contained almost no human T cells. Our data show that a relatively low overall incidence of human xenogeneic GVHD, even when high numbers of human PBL are injected, is the consequence of a dichotomy between mice with no or transient T-cell chimerism and a minority of mice with high-blood T-lymphocyte chimerism and GVHD mortality.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3440-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8099506-Animals, pubmed-meshheading:8099506-Antigens, CD3, pubmed-meshheading:8099506-Antigens, CD8, pubmed-meshheading:8099506-Bone Marrow, pubmed-meshheading:8099506-CD4-Positive T-Lymphocytes, pubmed-meshheading:8099506-Chimera, pubmed-meshheading:8099506-Graft vs Host Disease, pubmed-meshheading:8099506-HLA-DR Antigens, pubmed-meshheading:8099506-Humans, pubmed-meshheading:8099506-Immunohistochemistry, pubmed-meshheading:8099506-Immunophenotyping, pubmed-meshheading:8099506-Lymph Nodes, pubmed-meshheading:8099506-Mice, pubmed-meshheading:8099506-Mice, Inbred BALB C, pubmed-meshheading:8099506-Mice, Inbred C57BL, pubmed-meshheading:8099506-Mice, SCID, pubmed-meshheading:8099506-Spleen, pubmed-meshheading:8099506-T-Lymphocytes, pubmed-meshheading:8099506-Thymus Gland, pubmed-meshheading:8099506-Transplantation, Heterologous
pubmed:year
1993
pubmed:articleTitle
Immunohistology and immunocytology of human T-cell chimerism and graft-versus-host disease in SCID mice.
pubmed:affiliation
GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Immunologie, Munich, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't