Proliferation and apoptosis of human T cells during replicative senescence--a critical approach.
Normal human T lymphocytes growing in culture undergo replicative senescence. Previously, we have shown that in our conditions polyclonal T cells cease proliferation after about three weeks (Radziszewska et al., 1999, Cell Biol. Int. 23, 97-103). Now we present results of a more detailed analysis of in vitro growth as well as phenotypic changes of T cells. Cell cycle analysis showed that about 20% of cells were in the S phase until the 17th day of culture (young cells). The highest number of mitotic cells (phase G2/M; 10%) was observed during the first week of culture. All not dividing senescent cells were stopped in the G1 phase (after the 30th day of culture). The sub-G1 fraction which represents apoptotic cells did not exceed 8% during the whole period until the 30th day of culture. During in vitro T-cell growth, a rather rapid selection to CD3+ CD8+ cells occurs. In the presenescent (between the 17th and 30th day) and senescent populations the majority of cells (above 90%) were CD8 positive. We also have checked the expression of alpha-chain interleukin-2 (IL-2) receptor (CD25). In young and presenescent cells about one third of cells was CD25 positive, but only 15% in the pool of senescent cells. Immunoblotting analysis of p16 protein recognized previously as a marker of senescent T cells, showed its highest and transient expression in presenescent cells. A critical review of the polyclonal T cell replicative senescence model is presented.
Jaruga
E
E
Molecular Bases of Aging Laboratory, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa.
Skierski
J
J
Radziszewska
E
E
Sikora
E
E
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000502:physiology*
D015703:Antigens, CD; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015375:Receptors, Interleukin-2