Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T cells following repeated encounters with the same antigenic stimulus |
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Authors: | Valenzuela Hector F Effros Rita B |
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Institution: | Department of Pathology & Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, 90095, USA. |
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Abstract: | Induction of telomerase, the enzyme that extends telomeres, accompanies human T lymphocyte activation. Nevertheless, high proportions of memory T cells with shortened telomeres are present in vivo during HIV infection and aging. To elucidate the long-term telomerase dynamics in human T cells, longitudinal analyses were performed on T cells subjected to repeated encounters with an allogeneic cell line in long-term culture. Whereas CD4(+) and CD8(+) T cells showed similarly dramatic increases in telomerase activity following primary stimulation, by the fourth stimulation, telomerase activity was nearly undetectable in the CD8(+) subset, but remained high in the CD4(+) subset. In addition, we document the dependence of antigen-specific telomerase inducibility on CD28 and that the decline in telomerase activity parallels the loss of CD28 expression. These findings suggest stringent telomerase regulation in human T cells, a property that may ultimately contribute to telomere shortening, finite replicative potential, and loss of control over certain pathogens. |
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Keywords: | human T lymphocyte telomerase memory T cell CD28 |
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