Proliferation and apoptosis of human T cells during replicative senescence - a critical approach

• Autorzy: Jaruga E. , Skierski J. , Radziszewska E. , Sikora E.
• Języki publikacji: EN

Abstrakty

EN

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 untill 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.

Słowa kluczowe

EN

T lymphocyte; man; proliferation; human cell; phenotype change; apoptosis; growth; cell culture; T cell

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2000
• Tom: 47
• Numer: 2
• Opis fizyczny: p.293-300,fig.

Twórcy

autor

Jaruga E.

• Polish Academy of Sciences, L.Pasteura 3, 02-093 Warsaw, Poland

autor

Skierski J.

autor

Radziszewska E.

autor

Sikora E.

Bibliografia

• 1. Pawelec, G., Effros, R.B., Caruso, C., Remarque, E., Barnett, Y. & Solana, R. (1999) T cells and aging. Front. Biosci. 4, D216-269.
• 2. Akbar, A.N. & Salmon, M. (1997) Cellular environments and apoptosis: Tissue microenvironments control activated T-cell death. Immunol. Today 18, 72-76.
• 3. Cossarizza, A., Ortolani, C., Monti, D. & Franceschi, C. (1997) Cytometric analysis of immunosenescence. Cytometry 27, 297-313.
• 4. Franceschi, C., Valensin, S., Fagnoni, F., Barbi, C. & Bonafe, M. (1999) Biomarkers of immunosenescence within an evolutionary perspective: The challenge of heterogeneity and the role of antigenic load. Exp. Gerontol. 34, 911-921.
• 5. Effros, R.B. (1996) Insights on immunological aging derived from the T lymphocyte cellular senescence model. Exp. Gerontol. 31, 21-27.
• 6. Pan, C., Xue, B.H., Ellis, T.M., Peace, D.J. & Diaz, M.O. (1997) Changes in telomerase activity and telomere length during human T lymphocyte senescence. Exp. Cell. Res. 231, 346-353.
• 7. Erickson, S., Sangfelt, O., Heyman, M., Castro, J., Einhorn, S. & Grander, D. (1998) Involvement of the Ink4 proteins p16 and p15 in T-lymphocyte senescence. Oncogen 17, 595­602.
• 8. Effros, R.B. & Pawelec, G. (1997) Replicative senescence of T cells: Does the Hayflick Limit lead to immune exhaustion? Immunol. Today 18, 450-454.
• 9. Boucher, N., Dufeu-Duchesne, T., Vicaut, E., Farge, D., Effros, R.B. & Schachter, F. (1998) CD28 expression in T cell aging and human longevity. Exp. Gerontol. 33, 267-282.
• 10. Effros, R.B., Boucher, N., Porter, V., Zhu, X., Spaulding, C., Walford, R.L., Kronenberg, M., Cohen, D. & Schachter, F. (1994) Decline in CD28+ T cells in centenarians and in long-term T cell cultures: A possible cause for both in vivo and in vitro immunosenescence. Exp. Gerontol. 29, 601-609.
• 11. Spaulding, C., Guo, W. & Effros, R.B. (1999) Resistance to apoptosis in human CD8+ T cells that reach replicative senescence after multiple rounds of antigen-specific proliferation. Exp. Gerontol. 34, 633-644.
• 12. Radziszewska, E., Piwocka, K., Skierski, J. & Sikora, E. (1999) Uvc-induced cell death of Il-2-dependent human lymphocytes. Cell Biol. Int. 23, 97-103.
• 13. Pawelec, G., Rehbein, A., Haehnel, K., Merl, A. & Adibzadeh, M. (1997) Human T-cell clones in long-term culture as a model of immunosenescence. Immunol. Rev. 160, 31-42.
• 14. Pawelec, G., Wagner, W., Adibzadeh, M. & Engel, A. (1999) T cell immunosenescence in vitro and in vivo. Exp. Gerontol. 34, 419-429.
• 15. Berube, N.G., Smith, J.R. & Pereira-Smith, O.M. (1998) The genetics of cellular senescence. Am. J. Hum. Genet. 62, 1015-1019.
• 16. Hathcock, K.S., Weng, N.P., Merica, R., Jenkins, M.K. & Hodes, R. (1998) Cutting edge: Antigen-dependent regulation of telomerase activity in murine T cells. J. Immunol. 160, 5702-5706.
• 17. Hodes, R.J. (1999) Telomere length, aging, and somatic cell turnover. J. Exp. Med. 190, 153-156.
• 18. Pawelec, G., Adibzadeh, M., Rehbein, A., Hahnel, K., Wagner, W. & Engel, A. (2000) In vitro senescence models for human T lymphocytes. Vaccine 18, 1666-1674.
• 19. Effros, R.B. (1997) Loss of CD28 expression on T lymphocytes: A marker of replicative senescence. Dev. Comp. Immunol. 21, 471-478.
• 20. Potestio, M., Pawelec, G., Di Lorenzo, G., Candore, G., D'Anna, C., Gervasi, F., Lio, D., Tranchida, G., Caruso, C. & Romano, G.C. (1999) Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes. Exp. Gerontol. 34, 659-673.