UittrekselCellular senescence is believed to contribute to the aging process, and CD28-, CD57+ and KLRG1+ are cell surface markers that have been used to describe such “senescent cells” among human T-lymphocytes. By combining the expression of CD28, CD57 and KLRG1 on the cells, we showed that only CD57+ cells accumulated significantly in the elderly compared with the young people, notwithstanding their CD28 and KLRG1 phenotypes. Two distinct CD57+ subpopulations: CD28+CD57+ and CD28-CD57+ cells were distinguished. The expression of the senescence markers, p16 and p21 was higher in CD28+CD57+ cells than in other subpopulations in both age groups; the expression of p21 was age-related, which was not the case for p16. CMV infection and shifts in subpopulations were not likely explanations of the observed differences. Further characterization of subpopulations of CD8+ T-cells with markers of cellular senescence, apoptosis, differentiation and homing, favours CD28+CD57+ cells as senescent phenotypes. Differences in the expression of the homing and differentiation markers among CD28+CD57+ and CD28-CD57+ cells might indicate senescent cells of different origins.
Following the administration of chemotherapy to patients with breast or lung cancer, the number of non-senescent cells decreased faster than CD28+CD57+ and CD28-CD57+ cells. Also, a tendency of chemotherapy to induce senescent cells was observed among CD28+CD57+ cells. Compared to control persons, the CD8+ T-cell subpopulations of cancer patients presented an immunosenescence profile: we observed a lower CD8-/CD8+ ratio and higher proportion of CD28-CD57+ cells, persisting throughout the observation period. The differences in frequency of CD8+ subtypes correspond to those seen in the Immune Risk Profile and appear to be more pronounced with cancer disease advancement.
Concluding, this work provides further in vivo evidence on the existence of senescent T-cells, and their contribution to immunosenescence in aging and cancer.
|Datum Prijs||6 mei 2015|
|Begeleider||Ivan Bautmans (Promotor), Rose Njemini (Promotor), Tony Mets (Promotor), Christel Geerts (Jury), Christian Demanet (Jury), M Maggio (Jury) & Florence Chainiaux (Jury)|