Regulated expression of telomerase activity in human T lymphocyte development and activation.

Abstract

SummaryTelomerase, a ribonucleoprotein that is capable of synthesizing telomeric repeats,.is expressed in germline and malignant cells, and is absent in most normal human somatic cells. The selective expression of telomerase has thus been proposed to be a basis for the immortality of the germline and of malignant cells. In the present study, telomerase activity was analyzed in normal human T lymphocytes. It was found that telomerase is expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T lymphocytes, and at a low to undetectable level in peripheral blood T lymphocytes. Moreover, telomerase activity is highly inducible in peripheral T lymphocytes by activation through CD3 with or without CD28 costimulation, or by stimulation with phorbol myristate acetate (PMA)/ionomycin. The induction of telomerase by anti-CD3 plus anti-CD28 (anti-CD3/CD28) stimulation required ILNA and protein synthesis, and was blocked by herbimycin A, an inhibitor of Src protein tyrosine kinases. The immunosuppressive drug cyclosporin A selectively inhibited telomerase induction by PMA/ionomycin and by anti-CD3, but not by anti-CD3/CD28. Although telomerase activity in peripheral T lymphocytes was activation dependent and correlated with cell proliferation, it was not cell cycle phase restricted. These results indicate that the expression oftelomerase in normal human T lymphocytes is both developmentally regulated and activation induced. Telomerase may thus play a permissive role in T cell development and in determining the capacity of lymphoid cells for cell division and clonal expansion.

Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells

“…Concommitant upregulation of telomerase with FGF-2-induced NPC proliferation is consistent with the data reported for the hematopoietic system (Engelhardt et al, 1997). Telomerase has been shown to be upregulated in response to cytokine-induced proliferation and cell cycle activation in primitive resting hematopoietic cells that otherwise expressed low or undectable enzymatic activity (Weng et al, 1996), similarly as that we have observed for proliferating NPC. There is strong evidence that FGF2 e ectively modulates telomerase in vivo because telomerase activity is directly correlated to the level of FGF2 expression during brain development.…”

Telomerase activity in B-cell non-Hodgkin lymphomas is regulated by hTERT transcription and correlated with telomere-binding protein expression but uncoupled from proliferation

“…As within the group of lymphomas with constantly low telomerase activity (MCL, FL, DLBL) the proliferation varied substantially, a positive correlation of telomerase activity or hTERT expression with proliferation cannot be found. Thus, in contrast to reactive lymphocytes and the GC reaction, telomerase activity and hTERT expression in malignant lymphomas seem to be uncoupled from rates of proliferation (Buchkovich and Greider, 1996;Weng et al, 1996Weng et al, , 1997.…”

The Promoter of Human Telomerase Reverse Transcriptase Is Activated During Liver Regeneration and Hepatocyte Proliferation

“…Indeed, telomerase activity can be induced in human lymphocytes. 33 Thus, the activation of TERT in chronic hepatitis was thought to reflect an activation of telomerase in infiltrating lymphocytes. 34 Experimental systems to investigate the activation of hTERT in regenerating hepatocytes have been missing.…”