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Telomere erosion in memory T cells induced by telomerase inhibition at the site of antigenic challenge in vivo

Reed, JR; Vukmanovic-Stejic, M; Fletcher, JM; Soares, MVD; Cook, JE; Orteu, CH; Jackson, SE; ... Akbar, AN; + view all (2004) Telomere erosion in memory T cells induced by telomerase inhibition at the site of antigenic challenge in vivo. J EXP MED , 199 (10) 1433 - 1443. 10.1084/jem.20040178.

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Abstract

The extent of human memory T cell proliferation, differentiation, and telomere erosion that occurs after a single episode of immune challenge in vivo is unclear. To investigate this, we injected tuberculin purified protein derivative (PPD) into the skin of immune individuals and isolated responsive T cells from the site of antigenic challenge at different times. PPD-specific CD4(+) T cells proliferated and differentiated extensively in the skin during this secondary response. Furthermore, significant telomere erosion occurred in specific T cells that respond in the skin, but not in those that are found in the blood from the same individuals. Tissue fluid obtained front the site of PPD challenge in the skin inhibited the induction of the enzyme telomerase in T cells in vitro. Antibody inhibition studies indicated that type I interferon (IFN), which was identified at high levels in the tissue fluid and by immunohistology, was responsible in part for the telomerase inhibition. Furthermore, the addition of IFN-alpha to PPD-stimulated CD4(+) T cells directly inhibited telomerase activity in vitro. Therefore, these results suggest that the rate of telomere erosion in proliferating, antigen-specific CD4(+) T cells may be accelerated by type I IFN during a secondary response in vivo.

Type: Article
Title: Telomere erosion in memory T cells induced by telomerase inhibition at the site of antigenic challenge in vivo
DOI: 10.1084/jem.20040178
Keywords: senescence, inflammation, differentiation, proliferation, cytokines, REVERSE-TRANSCRIPTASE, REPLICATIVE SENESCENCE, CD28 EXPRESSION, APOPTOSIS, ACTIVATION, LYMPHOCYTES, LENGTH, INTERFERONS, INFECTION, MIGRATION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: http://discovery.ucl.ac.uk/id/eprint/150599
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