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Does in vitro replicative senescence of human CD8+ cells reflect the phenotypic changes observed during in vivo ageing?

100%
Brzezinska A.
Acta Biochimica Polonica
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2005
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vol. 52
|
issue 4
931-935
EN
Immunosenescence is viewed as a remodeling process with the exhaustion of naïve T cells and filling up of the immunological space with memory cells. In this study some phenotypic changes of CD8+ human cells during in vivo ageing were compared with those observed in long term cultures of lymphocytes derived from cord blood or from peripheral blood from donors of different age. Both in vivo and in vitro a significant decrease of the fraction of CD8+CD28+ cells was observed. Comparing the proportions of other T cell subpopulations (the CD4/CD8+ ratio, CD56, CD57, CD27) made it possible to conclude that replicative senescence in vitro partially reflects in vivo ageing.
2
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Curcumin induces cell death without oligonucleosomal DNA fragmentation in quiescent and proliferating human CD8+ cells

39%
Magalska A., Brzezinska A., Bielak-Zmijewska A., Piwocka K., Mosieniak G., Sikora E.
Acta Biochimica Polonica
|
2006
|
vol. 53
|
issue 3
531-538
EN
Cytotoxic CD8+ cells play an important role in determining host response to tumor, thus chemotherapy is potentially dangerous as it may lead to T cells depletion. The purpose of this study was to elucidate the propensity of quiescent and proliferating human CD8+ cells to undergo cell death upon treatment with curcumin, a natural dye in Phase I of clinical trials as a prospective chemopreventive agent. Methods: We treated human quiescent or proliferating CD8+ cells with 50 µM curcumin or irradiated them with UVC. Cell death symptoms such as decreased cell viability, chromatin condensation, activation of caspase-3 and specific DFF40/CAD endonuclease and oligonucleosomal DNA fragmentation were analyzed using MTT test, microscopic observation, Western blotting and flow cytometry. Results: Curcumin decreased cell viability, activated caspase-3 and decreased the level of DFF45/ICAD, the inhibitor of the DFF40/CAD endonuclease. However, this did not lead to oligonucleosomal DNA degradation. In contrast, UVC-irradiated proliferating, but not quiescent CD8+ cells revealed molecular and morphological changes characteristic for apoptosis, including oligonucleosomal DNA fragmentation. Curcumin can induce cell death in normal human lymphocytes both quiescent and proliferating, without oligonucleosomal DNA degradation which is considered as a main hallmark of apoptotic cell death. Taking into account the role of CD8+ cells in tumor response, their depletion during chemotherapy could be particularly undesirable.
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