Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Duftner, C; Dejaco, C; Hengster, P; Bijuklic, K; Joannidis, M; Margreiter, R; Schirmer, M.
Apoptotic effects of antilymphocyte globulins on human pro-inflammatory CD4+CD28- T-cells.
PLoS One. 2012; 7(3):e33939-e33939
Doi: 10.1371/journal.pone.0033939
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- Co-Autor*innen der Med Uni Graz
- Dejaco Christian
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- Abstract:
- Pro-inflammatory, cytotoxic CD4(+)CD28(-) T-cells with known defects in apoptosis have been investigated as markers of premature immuno-senescence in various immune-mediated diseases. In this study we evaluated the influence of polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F) on CD4(+)CD28(-) T-cells in vivo and in vitro. Surface and intracellular three colour fluorescence activated cell sorting analyses of peripheral blood mononuclear cells from 16 consecutive transplant recipients and short-term cell lines were performed. In vivo, peripheral levels of CD3(+)CD4(+)CD28(-) T-cells decreased from 3.7 ± 7.1% before to 0 ± 0% six hours after ATG-F application (P = 0.043) in 5 ATG-F treated but not in 11 control patients (2.9 ± 2.9% vs. 3.9 ± 3.0%). In vitro, ATG-F induced apoptosis even in CD4(+)CD28(-) T-cells, which was 4.3-times higher than in CD4(+)CD28(+) T-cells. ATG-F evoked apoptosis was partially reversed by the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) and prednisolon-21-hydrogensuccinate. ATG-F triggered CD25 expression and production of pro-inflammatory cytokines, and induced down-regulation of the type 1 chemokine receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L predominately in CD4(+)CD28(-) T-cells. In summary, in vivo depletion of peripheral CD3(+)CD4(+)CD28(-) T-cells by ATG-F in transplant recipients was paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine receptor down-regulation in CD4(+)CD28(-) T-cells only partly explain the underlying mechanism.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Antigens, CD28 - analysis
- Antigens, CD3 -
- Antigens, CD95 - metabolism
- Antilymphocyte Serum - immunology
- Apoptosis - drug effects
- CD4-Positive T-Lymphocytes - drug effects
- Caspases - metabolism
- Cytokines - biosynthesis
- Down-Regulation - drug effects
- Enzyme Activation - drug effects
- Female -
- Humans -
- Immunologic Factors - immunology
- Inflammation - immunology
- Interleukin-2 - metabolism
- Lymphocyte Depletion -
- Male -
- Middle Aged -
- Organ Transplantation -
- Receptors, Chemokine - metabolism
- Signal Transduction - drug effects
- Th1 Cells - drug effects
- Transendothelial and Transepithelial Migration - drug effects
- Young Adult -