“Molecular tuning of telomerase activity in highly differentiated human primary CD28−CD27− T cells”’
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1
University College London, United Kingdom
Telomerase is a RNA-dependent DNA polymerase re-expressed by T cells mounting an immune response upon antigenic stimulation. Highly differentiated CD28−CD27− (DN) T cells are an end-stage sub-population progressively accumulating in the elderly, in patients with autoimmune disorders, cancer and chronic viral diseases. These cells have short telomeres and show proliferative defects as a result of defective telomerase activity, due in part to active MAPK p38 signalling. Most interestingly telomerase activity and cell survival can be re-established following MAPK p38 blockade in DN T cells. Therefore key senescent features of the human memory T cell compartment are reversible. Although repeated antigenic stimulation is considered one of the main drivers of T cell senescence, metabolic dysfunctions and cytokine priming have been postulated to negatively impact the biochemical features of end-stage T cell sub-populations. However the molecular evidence for such a mechanism linking chronic inflammation, due to cytokines and/or metabolic impairment, and T cell senescence has not yet been elucidated. We report here an alternative mechanism regulating MAPK p38 activation in highly differentiated DN T cells. The mechanism described here provides a target for manipulation of telomerase activity in a T cell compartment specific manner, reducing the risk of malignancies. This may result in the design of novel immunotherapy strategies aimed at reversing T cell senescence and boosting T cell mediated immune responses.
Keywords:
T cells,
senescence,
Telomerase,
MAPK p38 signalling,
Metabolism
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune receptors and signaling
Citation:
Lanna
A,
Henson
SM,
Escors
D and
Akbar
AN
(2013). “Molecular tuning of telomerase activity in highly differentiated human primary CD28−CD27− T cells”’.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00016
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Received:
09 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Mr. Alessio Lanna, University College London, London, United Kingdom, a.lanna.11@ucl.ac.uk