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¹ Department of Immunology and Molecular Pathology, Division of Infection and Immunity, University College London, London, W1T 4JF, England, UK
² Department of Dermatology, Royal Free Hospital, London, NW3 2QG, England, UK
³ The Edward Jenner Institute for Vaccine Research, Compton, Berkshire, RG20 7NN, England, UK
⁴ Hepatobiliary Group, Institute of Cell and Molecular Science, Queen Mary's School of Medicine and Dentistry, The Royal London Hospital, London, E1 1BB, England, UK
⁵ Department of Rheumatology, Medical Research Council Centre for Immunoregulation, University of Birmingham, Birmingham, B15 2TT, England, UK

Address correspondence to Arne N. Akbar, Dept. of Immunology and Molecular Pathology, Div. of Infection and Immunity, University College London, 46 Cleveland St., London W1T 4JF, England, UK. Phone: 44-207-679-9214; Fax: 44-207-679-9119; email: a.akbar{at}ucl.ac.uk

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- 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.

Key Words: senescence • inflammation • differentiation • proliferation • cytokines

Abbreviations used in this paper: BCG, Bacille Calmette-Guerin; flow-FISH, flow cytometric detection of fluorescence in situ hybridization; HDA, heteroduplex analysis; MT, Mantoux test; PPD, purified protein derivative; SB, suction blister.

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