Different rates of telomere shortening and telomerase activity reduction in CD8 T and CD16 NK lymphocytes with ageing.

Telomeres are specialised structures located at the end of eukaryotic chromosomes, that get short during progressive cell divisions. Therefore, telomere may be an indicator of the mitotic history of a cell and it is also a determining factor for the residual cell life span. One mechanism, compensating for the telomere erosion, involves the induction of telomerase, a ribonucleoprotein-enzyme able to synthesize telomeric DNA repeats.

Telomere length and telomerase activity: effect of ageing on human NK cells.

Telomeres are repeats of TTAGGG sequences located at the end of eukaryotic chromosomes. They are essential for stabilisation and protection of chromosomal ends and for the regulation of cell replicative capacity. Due to the end-replication defect of DNA polymerase, telomeres shorten progressively with each cell division and telomere length may be an indicator of the replicative history of a cell.

Chemokine production by natural killer cells from nonagenarians.

In this study we investigated whether purified NK cells, derived from a group of nonagenarian healthy subjects, were able to produce the chemokines MIP-1alpha, RANTES and IL-8, and also characterized the effect of IL-12 or IL-2 immunomodulatory cytokines (that are among the most effective inducers of NK lytic activity and soluble factor secretion) on the induction, in vitro, of these chemokines and on the modulation of the corresponding receptors. This study provides evidence that human NK cells from healthy subjects over 90 years old retain the ability to synthesize MIP-1alpha, Rantes and IL-8 chemotactic cytokines, that NK cells isolated from these subjects can be activated to significantly up-regulate the production of these chemokines in response to stimulation by IL-12 or IL-2 cytokines (even though production remains lower than that observed in young subjects), and that NK cells express the corresponding chemokine receptors.

RANTES and MIP-1alpha production by T lymphocytes, monocytes and NK cells from nonagenarian subjects.

While numerous previous studies have investigated age-related changes of cytokine production, little is known about chemokines, the importance of which in regulating immune response is becoming increasingly evident. In this study, a group of healthy subjects over 90 years old is compared to a group of young subjects, we evaluated the ability of monocytes, T lymphocytes and NK cells: (1) to produce RANTES and MIP-1alpha, either in basal conditions or after stimulation with, respectively, LPS, anti-CD3 MoAb and IL-2; (2) to express the corresponding chemokine receptors (CCR1, CCR3, CCR5). We demonstrate that: (a) monocytes, T lymphocytes and NK cells spontaneously produced detectable amounts of chemokines, both in young and old subjects; (b) monocyte-dependent RANTES and MIP-1alpha production induced by LPS was up-regulated in nonagenarian subjects as anti-CD3-induced secretion from T cells; (c) RANTES and MIP-1alpha production by IL-2 stimulated NK cells was reduced in elderly subjects; (d) CCR1, CCR3 and CCR5 were widely expressed on monocytes, but less expressed on T lymphocytes and NK cells.