Telomere donors
Intercellular telomere transfer prolongs the life of T cells
Ekaterina Petrova, PCR.news
Telomeres are chains of repeating TTAGGG sequences that protect the ends of chromosomes from damage during division. With each division, telomeres shrink, which eventually leads to cell aging — these are two of the nine key signs of aging of the body. In the stem, germ and immune cells of the body, a special enzyme telomerase works, which grows the ends of the telomere after division and prolongs the life of the cell. Telomerase activity decreases with age.
An international team led by scientists from University College London has discovered another mechanism of telomere elongation in T cells. It turned out that antigen-presenting cells (APC), which include B cells, dendritic cells and macrophages, transmit vesicles with telomeres to some T cells (primarily naive and central memory cells).
Scientists investigated in vitro interaction of antigen-presenting cells and T-lymphocytes. These cells form an "immunological synapse": the APC, after meeting with the antigen, exposes this antigen on its surface — T cells recognize such antigens with the help of receptors, bind to the APC and are activated to begin attacking the pathogen. Unexpectedly, the researchers found telomere elongation in T cells after the formation of such a synapse, and at the same time telomere contraction in the APC. This happens regardless of the action of telomerase — in cells with a knockout of this enzyme, as the authors of the work showed, telomeres can be lengthened due to transmission from the APC. Such a form of intercellular communication has not been known until now.
It turned out that upon contact with T cells, APC cleaves shelterin, a protein complex that protects telomeres. The released telomeres are cleaved by the TZAP protein, and they are transported in extracellular vesicles through an immunological synapse into T cells. At the same time, vesicles with telomeres also contain a recombination factor Rad51, which allows telomeres to be attached to the ends of T-cell chromosomes. As a result, the chromosomes lengthen by about 3000 base pairs. This protects T cells from aging before clonal division begins, providing long-term immune protection.
The authors also found out that if intercellular vesicles with telomeres are isolated and added to T cells, this will prolong their life. Telomere-acquiring T cells become stem and/or central long-lived memory cells, while other T cells age.
"The phenomenon of telomere transfer between immune cells complements the Nobel Prize-winning discovery of telomerase and shows that cells are able to exchange telomeres in order to regulate the length of chromosomes before telomerase begins to act. Perhaps aging can be slowed down or cured by simply transplanting telomeres," comments the first author of the article Alessio Lanna, professor of the Medical Department of University College London.
The authors also investigated telomere transfer in vivo, for which they injected mice with APC loaded with antigen into the paw pad, and dye-labeled T cells intravenously, and in the mouse body T cells also acquired telomeres from APC. Another experiment in mice showed that the addition of telomeric vesicles to the vaccination protocol increases the duration of immune protection against the influenza virus.
Article by Lanna et al. An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory is published in the journal Nature Cell Biology.
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