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Mechanism of telomerase induction during T cell activation
A G Bodnar1, N W Kim, R B Effros
1Geron Corporation, Menlo Park, California 94025, USA.
Experimental Cell Research
|October 10, 1996
Summary
Telomerase activity increases transiently during T cell activation but does not prevent telomere shortening. This telomere maintenance mechanism is linked to T cell signaling pathways.
Area of Science:
- Cellular Biology
- Molecular Biology
- Immunology
Background:
- Telomere shortening acts as a mitotic clock, leading to replicative senescence.
- Telomerase, an enzyme that maintains telomere length, is typically absent in somatic cells but present in immortal cells.
- Previous studies indicated low telomerase activity in peripheral blood mononuclear cells (PBMC) and hematopoietic cells, with a reported increase during T cell activation.
Purpose of the Study:
- To investigate the dynamics of telomerase activity during T cell activation.
- To elucidate the mechanism of telomerase induction in activated T cells.
- To determine the role of telomerase in preventing telomere shortening in long-term T cell cultures.
Main Methods:
- Measuring telomerase activity in activated peripheral blood mononuclear cells (PBMC).
- Analyzing the levels of human telomerase RNA (hTR) during T cell activation.
- Assessing telomere length in long-term T cell cultures.
- Investigating the requirement of DNA synthesis using aphidicolin.
- Examining the role of protein kinase C (PKC) signaling pathway by inhibiting it with bisindolylmaleimide.
Main Results:
- The increase in telomerase activity during T cell activation was transient and did not prevent telomere attrition in long-term cultures.
- Telomerase induction correlated with increased levels of hTR, the RNA component of human telomerase.
- Telomerase induction occurred independently of DNA synthesis and early transmembrane signals.
- The induction of telomerase was linked to the T cell signal transduction pathway, specifically involving protein kinase C.
Conclusions:
- Transient telomerase activation during T cell activation is insufficient to maintain telomere length in long-term cultures.
- Telomerase induction involves increased hTR levels and is regulated by T cell signaling pathways, including protein kinase C.
- These findings suggest that telomere maintenance in activated T cells is complex and not solely dependent on transient telomerase activity.