title: Resistance to tumor necrosis factor-alpha-induced apoptosis in human T-lymphotropic virus type I-infected T cell lines.
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 TNFR2 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.
authors.affiliation: School of Medical Technology, College of Medicine, National Taiwan University, Taipei 100, Taiwan, Republic of China. ycyang@ha.mc.ntu.edu.tw
authors.forename: Ya-Chien
authors.initials: YC
authors.lastname: Yang
authors.forename: Tsuey-Ying
authors.initials: TY
authors.lastname: Hsu
authors.forename: Rong-Hwa
authors.initials: RH
authors.lastname: Lin
authors.forename: Ih-Jen
authors.initials: IJ
authors.lastname: Su
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Chen
authors.forename: Czau-Siung
authors.initials: CS
authors.lastname: Yang
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D004351:Drug Resistance; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha