Resistance to Tumor Necrosis Factor-Alpha-Induced Apoptosis in Human T- Lymphotropic Virus Type I-Infected T Cell Lines
Resource
AIDS RESEARCH AND HUMAN RETROVIRUSES v.18 n.3 pp.207-212
Journal
AIDS RESEARCH AND HUMAN RETROVIRUSES
Journal Volume
v.18
Journal Issue
n.3
Pages
207-212
Date Issued
2002
Date
2002
Author(s)
YANG, YA-CHIEN
HSU, TSUEY-YING
YANG, CZAU-SIUNG
Abstract
Induction of apoptosis of virus-infected cells is an important host cell defense mechanism. It is well documented that T cells may undergo apoptosis due to interactions between Fas and Fas ligand (FasL). In addition, signals that induce apoptosis in T cells can result from interaction of tumor necrosis factor (TNF)-alpha with TNF receptors (TNFRs ) . It has been shown that human T cell lines expressing HTLV- I have decreased sensitivity to Fas-mediated apoptosis. The susceptibility of HTLV-I-infected cells to TNF-alpha- induced apoptosis remains to be elucidated. In the present study, we examined the expression of TNFRs on HTLV-I- infected T cell lines that expressed T-cell activation markers and thus phenotypically resemble activated T cells. Different from primary activated T cells that expressed both TNFRs, none of the five HTLV-I- infected T cell lines studied had detectable TNFR1 and only three had TNFR 2 on their cell surfaces, although, the RNA transcripts of both TNFR genes could be detected via reverse transcription- polymerase chain reaction in these cell lines. The T cell blasts, which we activated in vitro, were sensitive to apoptosis induced by TNF-alpha and by antibodies to TNFR1 and /or TNFR2. However, all of the HTLV-I-infected cell lines expressing TNFR2 were resistant to TNF-alpha-mediated apoptosis. These findings suggest that HTLV-I infection may interfere with the autonomous suicide programs of T cells, not only Fas/FasL but also TNFRs/TNF-alpha pathways, to prolong the life of the infected cells. This may contribute to viral persistence and favor survival and subsequent expansion of dysregulated infected T cells with the potential to produce HTLV-I- associated autoimmune-like diseases or malignancies.
Subjects
BCL-2 EXPRESSION
GENE-EXPRESSION
LEUKEMIA-VIRUS
B-CELLS
ACTIVATION
RETROVIRUS
SDGs