Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1998-2-17
pubmed:abstractText
Apoptosis has been suggested to account for loss of CD4+ T-cells in HIV infected individuals. Aside from MHC II dependent superantigens no mediator for preferential apoptosis of CD4+ T-cell has been described. However, the expression of TNF-alpha is increased in HIV+ patients. Additionally, TNF-alpha is known as a potent inducer of apoptosis in a variety of cell types. We therefore investigated the capacity of TNF-alpha to mediate apoptosis in vitro preferentially in CD4+ T-cells from HIV+ individuals. In the presence of TNF-alpha, CD4+ T-cells from HIV+ individuals with more than 200 CD4+ T-cells/microl (classified CDC A1, A2, B1, B2) could be significantly depleted by apoptosis without a reduction of CD8+ T-cells. In cells from patients with less than 100 CD4+ T-cells/microl (classified CDC C3), TNF-alpha mediated apoptosis was not apparent due to an already immensely elevated rate of apoptosis observed in the absence of TNF-alpha. Here we demonstrate cord blood mononuclear cells as a model for apoptosis since these cells develop apoptosis at a similar rate as that of PBMC in HIV+ patients. More than 50% of TNF-alpha stimulated CD4+ cord blood T-cells were depleted within 3 days by apoptosis, whereas CD8+ T-cells, B-cells and NK-cells were not affected. In PBMC from healthy adults, a preferential loss of CD4+ T-cells mediated by TNF-alpha was not observed. A reduced production of IFN-gamma was observed in mononuclear cells from newborns and from HIV+ patients. Moreover, IFN-gamma and IL-2 could prevent TNF-alpha mediated apoptosis. Therefore, a reduced Th1-cell-function may contribute to TNF-alpha mediated apoptosis of CD4+ T-cells from these donor groups. Taken together, the data suggest that TNF-alpha probably is a mediator of the loss of CD4+ T-cells in HIV infected patients in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0949-2321
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
249-58
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9374446-Adult, pubmed-meshheading:9374446-Antibodies, Monoclonal, pubmed-meshheading:9374446-Apoptosis, pubmed-meshheading:9374446-B-Lymphocytes, pubmed-meshheading:9374446-CD4-CD8 Ratio, pubmed-meshheading:9374446-CD4-Positive T-Lymphocytes, pubmed-meshheading:9374446-Cells, Cultured, pubmed-meshheading:9374446-Fetal Blood, pubmed-meshheading:9374446-Flow Cytometry, pubmed-meshheading:9374446-HIV Infections, pubmed-meshheading:9374446-HIV Seronegativity, pubmed-meshheading:9374446-HIV Seropositivity, pubmed-meshheading:9374446-HIV-1, pubmed-meshheading:9374446-Humans, pubmed-meshheading:9374446-Infant, Newborn, pubmed-meshheading:9374446-Interferon-gamma, pubmed-meshheading:9374446-Interleukin-2, pubmed-meshheading:9374446-Killer Cells, Natural, pubmed-meshheading:9374446-Lymphocyte Depletion, pubmed-meshheading:9374446-Models, Immunological, pubmed-meshheading:9374446-Reference Values, pubmed-meshheading:9374446-Tumor Necrosis Factor-alpha
pubmed:year
1996
pubmed:articleTitle
TNF-alpha mediated apoptosis of CD4 positive T-lymphocytes. A model of T-cell depletion in HIV infected individuals.
pubmed:affiliation
Universit-atsklinik Frankfurt, Medizinische Klinik III, Theodor-Stern-Kai 7, Frankfurt D-60590, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't