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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-11-4
pubmed:abstractText
Syngeneic pancreatic islet grafts in diabetic NOD mice are infiltrated by mononuclear leukocytes, beta-cells are selectively destroyed, and autoimmune diabetes recurs. This model was used to identify islet graft-infiltrating mononuclear leukocytes associated with beta-cell destruction and diabetes recurrence. We compared cell surface antigen and cytokine-producing phenotypes of mononuclear leukocytes in islet grafts from NOD mice that were protected from diabetes recurrence by complete Freund's adjuvant (CFA) administration (beta-cell nondestructive insulitis) and in islet grafts from control phosphate-buffered saline (PBS)-injected NOD mice (beta-cell destructive insulitis). Islet grafts from CFA-injected mice contained fewer CD4+ and CD8+ cells and more B cells; also fewer interferon gamma (IFN-gamma), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-alpha)-positive cells and more IL-4 and IL-10 positive cells. By performing two-color immunostaining of cell surface antigens and intracellular IFN-gamma, we found that IFN-gamma positive cells in islet grafts from CFA- and PBS-injected mice were approximately equally divided between CD4+ and CD8+ T-cell subsets. Also, the frequencies of both CD4+ IFN-gamma + and CD8+ IFN-gamma + cells were decreased in islet grafts from CFA-injected mice. These findings suggest that destruction of beta-cells in syngeneic islets transplanted into NOD mice is promoted by cells producing Th1-type cytokines (IFN-gamma, IL-2, and TNF-alpha) and prevented by cells producing TH2-type cytokines (IL-4 and IL-10). Furthermore, both CD4+ and CD8+ IFN-gamma-producing T-cells in the islet grafts appear to be involved in beta-cell destruction and diabetes recurrence.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1350-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8826970-Animals, pubmed-meshheading:8826970-CD4-Positive T-Lymphocytes, pubmed-meshheading:8826970-CD8-Positive T-Lymphocytes, pubmed-meshheading:8826970-Cytokines, pubmed-meshheading:8826970-Diabetes Mellitus, Type 1, pubmed-meshheading:8826970-Female, pubmed-meshheading:8826970-Flow Cytometry, pubmed-meshheading:8826970-Hypoglycemic Agents, pubmed-meshheading:8826970-Immunohistochemistry, pubmed-meshheading:8826970-Insulin, Long-Acting, pubmed-meshheading:8826970-Interferon-gamma, pubmed-meshheading:8826970-Interleukin-10, pubmed-meshheading:8826970-Interleukin-2, pubmed-meshheading:8826970-Interleukin-4, pubmed-meshheading:8826970-Islets of Langerhans Transplantation, pubmed-meshheading:8826970-Mice, pubmed-meshheading:8826970-Mice, Inbred NOD, pubmed-meshheading:8826970-Reference Values, pubmed-meshheading:8826970-Spleen, pubmed-meshheading:8826970-T-Lymphocyte Subsets, pubmed-meshheading:8826970-Transplantation, Isogeneic, pubmed-meshheading:8826970-Tumor Necrosis Factor-alpha
pubmed:year
1996
pubmed:articleTitle
Both CD4+ and CD8+ T-cells in syngeneic islet grafts in NOD mice produce interferon-gamma during beta-cell destruction.
pubmed:affiliation
Department of Medicine, University of Alberta, Edmonton, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't