Resistance to Fas-Mediated Apoptosis of Human T-Cell Lines Expressing Human T-Lymphotropic Virus Type-2 (HTLV-2) Tax Protein

Abstract

The susceptibility to Fas-mediated apoptosis was evaluated in seven T-cell lines (two infected with HTLV-2, one with HTLV-1, and four HTLV-free) as well as in Jurkat cells transfected with a Tax-2 expressing vector. Fas-mediated apoptosis was significantly reduced in the HTLV-1- and HTLV-2-infected lines in comparison with the HTLV-free lines regardless of the surface expression of Fas antigen (which was no different in the infected and uninfected cells). Fas-mediated apoptosis was also significantly inhibited in Jurkat cells transfected with the Tax-2 expressing vector without any modification in Fas expression. There was significantly more antiapoptotic Bcl-x(L) mRNA and protein in the transfected than in the untransfected Jurkat T cells. In conclusion, our results suggest that HTLV-2 is capable of inhibiting Fas-mediated apoptosis by means of a mechanism involving the tax-2 gene and probably the expression of bcl-x(L) messenger and protein.

Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Tax Oncoproteins Modulate Cell Cycle Progression and Apoptosis

“…Although Tax2 shows a high degree of homology at the amino acid level compared to Tax1, distinct phenotypes for Tax2 have been reported (17,35,42,70). In these studies we show that Tax1 is more effective at inhibiting cellular replication kinetics of T lymphoid cells and in transcriptionally activating p21 expression compared to Tax2.…”

“…Tax1 has been reported to increase resistance of cell lines to apoptosis (12,45,51,63,70). Tax1 has recently been shown to bind and alter the activity of Top1 in vitro (58,69).…”

Cross-Regulation of T Cell Growth Factor Expression by p53 and the Tax Oncogene

“…Both p53 and Tax previously have been shown to induce apoptosis in lymphoid cells, although the precise mechanism of their effects remains to be determined (45)(46)(47). As shown in Fig.…”

An inducible caspase 9 safety switch for T-cell therapy

“…31,32 Jurkat cells and MT-2 cells were transduced with iFas and iCasp9 M with similar efficiencies (92% vs 84% in Jurkat, 76% vs 70% in MT-2) and were cultured in the presence of 10 nM CID for 8 hours. Annexin-V staining showed that although iFas and iCasp9 M induced apoptosis in an equivalent number of Jurkat cells (56.4% Ϯ 15.6% and 57.2% Ϯ 18.9%, respectively), only activation of iCasp9 M resulted in apoptosis of MT-2 cells (19.3% Ϯ 8.4% and 57.9% Ϯ 11.9% for iFas and iCasp9 M , respectively; Figure 5C).…”