Stimulation of the CD2 Receptor Pathway Induces Apoptosis in Human T Lymphotropic Virus Type I-Infected Cell Lines

Guyot, Deborah J.; Trask, O. Joseph; Andrews, Janice M.; Newbound, Garret C.; Lairmore, Michael Dale

doi:10.1097/00042560-199604010-00001

Cited by 8 publications

(5 citation statements)

References 48 publications

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“…Fresh leukemic cells from ATL patients as well as HTLV-1-transformed T-cell lines were reported to be sensitive to CD95 mediated (Debatin et al, 1990(Debatin et al, , 1993 and activation induced cell death (Guyot et al, 1996;Leno et al, 1995). Apoptotic eects of HTLV-1 infection have been reported in conjunction with the associated degenerative disorders (Kalden and Gay, 1994;Muller et al, 1995;Seto et al, 1995;Yoshiki, 1995).…”

Section: Discussionmentioning

confidence: 99%

ICE-proteases mediate HTLV-I Tax-induced apoptotic T-cell death

et al. 1997

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The Tax protein of Human T-cell leukemia virus type 1 (HTLV-1) is important for the T-cell immortalizing properties of this virus in vitro and is considered to be responsible for the early stages of leukemogenesis in infected hosts. Tax can upregulate expression of TNF-a and TNF-b, as well as potentiate apoptosis in activated Tcells and in serum starved murine ®broblasts. To examine the role of CD95 (APO-1/Fas) and ICE-proteases in Taxmediated active T-cell death, Jurkat T cells expressing (APO S ) or lacking (APO R ) cell surface expression of CD95 (APO-1/Fas) were genetically modi®ed to express hormone-inducible HTLV-1 Tax constructs. Hormoneinducible action of Tax alone was sucient to promote programmed cell death in CD95-expressing Jurkat T-cell clones. In contrast, clones lacking CD95 surface expression were resistant to the antiproliferative action of Tax. Both APO S and APO R clones exhibited Tax-dependent upregulation of CD95 ligand and TNF-a. Blocking experiments suggested that while the apoptotic action of Tax critically required ICE-protease function it was largely independent of cell surface interaction of CD95 ligand or TNF-a with their corresponding receptors. These observations strongly implicate ICE-proteases in Taxinduced T-cell death, and suggest a possible involvement of CD95 in this process.

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Section: Discussionmentioning

confidence: 99%

ICE-proteases mediate HTLV-I Tax-induced apoptotic T-cell death

et al. 1997

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“…Several reports have demonstrated that HTLV-I-infected T cells can be induced to undergo apoptosis. Fresh mononuclear cells from ATL patients are activated (CD25 ϩ ) and sensitive to CD95-mediated apoptosis (55), and IL-2-dependent HTLV-Iinfected T-cell lines are susceptible to anti-CD95-induced (54) and activation (CD2)-induced apoptosis (103). These apparently conflicting results may be due in part to differences in anti-CD95 antibodies and the concentrations used.…”

Section: Programmed Cell Death In Htlv-i-infected T Cellsmentioning

confidence: 99%

“…This would then lead to enhanced viral production and possibly to infection of more T cells. Whereas antibody-mediated activation of the CD2 pathway may result in apoptosis in HTLV-I-infected T cells (103,305), it is unclear whether this occurs after CD2-CD58 interaction.…”

Section: Activation Of Non-virus-specific T Cellsmentioning

confidence: 99%

Mechanisms of T-Cell Activation by Human T-Cell Lymphotropic Virus Type I

Höllsberg

1999

Microbiol Mol Biol Rev

110

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SUMMARY The interactions between human T-cell lymphotropic virus type I (HTLV-I) and the cellular immune system can be divided into viral interference with functions of the infected host T cell and the subsequent interactions between the infected T cell and the cellular immune system. HTLV-I-mediated activation of the infected host T cell is induced primarily by the viral protein Tax, which influences transcriptional activation, signal transduction pathways, cell cycle control, and apoptosis. These properties of Tax may well explain the ability of HTLV-I to immortalize T cells. It is not clear, though, how HTLV-I induces T-cell transformation (interleukin-2 [IL-2] independence). Recent evidence suggests that Tax may promote the G1- to S-phase transition, although this may involve additional proteins. A role for other viral proteins that may constitutively activate the IL-2 receptor pathway has also been suggested. By virtue of their activated state, HTLV-I-infected T cells can nonspecifically activate resting, uninfected T cells via virus-mediated upregulation of adhesion molecules. This may favor viral dissemination. Moreover, the induction of a remarkably high frequency of antiviral CD8+ T cells does not appear to eliminate the infection. Indeed, individuals with a high frequency of virus-specific CD8+ T cells have a high viral load, indicating a state of chronic immune system stimulation. Thus, while an activated immune system is needed to eradicate the infection, the spread of the HTLV-I is also accelerated under these conditions. A detailed knowledge of the molecular interactions between virus-specific CD8+ T cells and immunodominant viral epitopes holds promise for the development of specific antiviral therapy.

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“…Recent data have shown that human Tlymphotropic virus type 1 (HTLV-1) interferes with Fas-mediated apoptosis. It has been suggested that a modification of the apoptotic pathway may be a pathogenic mechanism in HTLV-1-related lymphoproliferative, neurological and autoimmune diseases in humans (Arai et al, 1998;Copeland et al, 1994;Debatin et al, 1990;Guyot et al, 1996) and animal models (Kishi et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2001

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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.

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Stimulation of the CD2 Receptor Pathway Induces Apoptosis in Human T Lymphotropic Virus Type I-Infected Cell Lines

Cited by 8 publications

References 48 publications

ICE-proteases mediate HTLV-I Tax-induced apoptotic T-cell death

ICE-proteases mediate HTLV-I Tax-induced apoptotic T-cell death

Mechanisms of T-Cell Activation by Human T-Cell Lymphotropic Virus Type I

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

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