Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T cells following repeated encounters with the same antigenic stimulus

Clin Immunol. 2002 Nov;105(2):117-25. doi: 10.1006/clim.2002.5271.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen-Presenting Cells / immunology
  • CD28 Antigens / metabolism*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / enzymology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / enzymology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Division
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Enzyme Induction
  • Humans
  • Immunologic Memory
  • Isoantigens / administration & dosage
  • Kinetics
  • Lymphocyte Activation
  • Telomerase / biosynthesis
  • Telomerase / metabolism*


  • CD28 Antigens
  • Isoantigens
  • Telomerase