Telomere erosion in memory T cells induced by telomerase inhibition at the site of antigenic challenge in vivo.
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 from 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.
Reed
John R
JR
Dept. of Immunology and Molecular Pathology, Div. of Infection and Immunity, University College London, 46 Cleveland St., London W1T 4JF, England, UK.
Vukmanovic-Stejic
Milica
M
Fletcher
Jean M
JM
Soares
Maria Vieira D
MV
Cook
Joanne E
JE
Orteu
Catherine H
CH
Jackson
Sarah E
SE
Birch
Katie E
KE
Foster
Graham R
GR
Salmon
Mike
M
Beverley
Peter C L
PC
Rustin
Malcolm H A
MH
Akbar
Arne N
AN
D001500:BCG Vaccine / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D017404:In Situ Hybridization, Fluorescence; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*; D019098:Telomerase / Q000187:drug effects* / Q000276:immunology*; D016615:Telomere / Q000235:genetics*
D001500:BCG Vaccine; D004791:Enzyme Inhibitors; D019098:Telomerase