Switch to
Predicate | Object |
---|---|
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
|