Telomere Science Library

Publications, Presentations, and Videos
about the Nobel-Prize Winning Science of Telomere Biology

Telomerase-Based Pharmacologic Enhancement of Antiviral Function of Human CD8+ T Lymphocytes1

Steven Russell Fauce, Beth D. Jamieson , Allison C. Chin, Ronald T. Mitsuyasu , Stan T. Parish, Hwee L. Ng, Christina M. Ramirez Kitchen, Otto O. Yang, Calvin B. Harley , and Rita B. Effros. Department of Pathology and Laboratory Medicine and Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095; Geron, Menlo Park, CA 94025; and Department of Biostatistics, University of California-Los Angeles, School of Public Health, Los Angeles, CA 90095

Telomerase reverse transcribes telomere DNA onto the ends of linear chromosomes and retards cellular aging. In contrast to most normal somatic cells, which show little or no telomerase activity, immune cells up-regulate telomerase in concert with activation. Nevertheless, during aging and chronic HIV-1 infection, there are high proportions of dysfunctional CD8+ CTL with short telomeres, suggesting that telomerase is limiting. The present study shows that exposure of CD8+ T lymphocytes from HIV-infected human donors to a small molecule Telomerase Activator (TAT2) modestly retards telomere shortening, increases proliferative potential, and, importantly, enhances cytokine/chemokine production and antiviral activity. The enhanced antiviral effects were abrogated in the presence of a potent and specific telomerase inhibitor, suggesting that TAT2 acts primarily through telomerase activation. Our study is the first to use a pharmacological telomerase-based approach to enhance immune function, thus directly addressing the telomere loss immunopathologic facet of chronic viral infection.

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