Membrane lymphotoxin is required for resistance to Theiler's virus infection

Xiaoqi Lin, Xiaoxing Ma, Moses Rodriguez, Xuan Feng, Laurie Zoecklein, Yang Xin Fu*, Raymond P. Roos

*Corresponding author for this work

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Lymphotoxin (LT) and tumor necrosis factor (TNF) are important in immune system development and function. LT consists of soluble LT-α3, which binds to TNF-R1 and TNF-R2, and membrane LT-α1β2, which binds to LT-β-R. We investigated the role of LT and TNF in disease induced by Daniel's (DA) strain of Theiler's murine encephalomyelitis virus (TMEV) since the immune response is believed to be important in both resistance to DA infection as well as mediation of virus-induced demyelination. DA persisted and induced inflammatory demyelination in LT-α-/- (but not TNF-/-) weanling mice of a normally resistant haplotype (C57BL/6), suggesting that LT, but not TNF, is critical for resistance to DA infection. This activity of LT depends on membrane LT-α1β2 and not soluble LT-α3, since DA virus persisted and induced inflammatory demyelination in LT-β-R-/-, but not TNF-R1-/- or TNF-R2-/-, mice. The LT-α-/- and LT-β-R-/- mice failed to mount a virus-specific cytotoxic T cell response. Treatment of weanling C57BL/6 mice with LT-β-R-lg, which blocks membrane LT activity, failed to increase susceptibility, suggesting that the LT effect is related to its action on immune system development which is fixed by 3 weeks of age. Our data suggest that membrane LT is important in resistance to DA infection (possibly through interference with CD8+ T cell development and function). There was relatively little demyelination associated with inflammation in LT-α-/- and LT-β-R-/- mice compared to susceptible SJL mice, suggesting the possibility that LT plays a role in mediating demyelination.

Original languageEnglish (US)
Pages (from-to)955-962
Number of pages8
JournalInternational Immunology
Volume15
Issue number8
DOIs
StatePublished - Aug 1 2003

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Theilovirus
Lymphotoxin-alpha
Virus Diseases
Membranes
Tumor Necrosis Factor-alpha
Demyelinating Diseases
Viruses
Immune System

Keywords

  • Cytokine
  • Cytotoxic T lymphocyte
  • Demyelination
  • Lymphotoxin
  • Theiler's virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Lin, X., Ma, X., Rodriguez, M., Feng, X., Zoecklein, L., Fu, Y. X., & Roos, R. P. (2003). Membrane lymphotoxin is required for resistance to Theiler's virus infection. International Immunology, 15(8), 955-962. https://doi.org/10.1093/intimm/mcg094
Lin, Xiaoqi ; Ma, Xiaoxing ; Rodriguez, Moses ; Feng, Xuan ; Zoecklein, Laurie ; Fu, Yang Xin ; Roos, Raymond P. / Membrane lymphotoxin is required for resistance to Theiler's virus infection. In: International Immunology. 2003 ; Vol. 15, No. 8. pp. 955-962.
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abstract = "Lymphotoxin (LT) and tumor necrosis factor (TNF) are important in immune system development and function. LT consists of soluble LT-α3, which binds to TNF-R1 and TNF-R2, and membrane LT-α1β2, which binds to LT-β-R. We investigated the role of LT and TNF in disease induced by Daniel's (DA) strain of Theiler's murine encephalomyelitis virus (TMEV) since the immune response is believed to be important in both resistance to DA infection as well as mediation of virus-induced demyelination. DA persisted and induced inflammatory demyelination in LT-α-/- (but not TNF-/-) weanling mice of a normally resistant haplotype (C57BL/6), suggesting that LT, but not TNF, is critical for resistance to DA infection. This activity of LT depends on membrane LT-α1β2 and not soluble LT-α3, since DA virus persisted and induced inflammatory demyelination in LT-β-R-/-, but not TNF-R1-/- or TNF-R2-/-, mice. The LT-α-/- and LT-β-R-/- mice failed to mount a virus-specific cytotoxic T cell response. Treatment of weanling C57BL/6 mice with LT-β-R-lg, which blocks membrane LT activity, failed to increase susceptibility, suggesting that the LT effect is related to its action on immune system development which is fixed by 3 weeks of age. Our data suggest that membrane LT is important in resistance to DA infection (possibly through interference with CD8+ T cell development and function). There was relatively little demyelination associated with inflammation in LT-α-/- and LT-β-R-/- mice compared to susceptible SJL mice, suggesting the possibility that LT plays a role in mediating demyelination.",
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Lin, X, Ma, X, Rodriguez, M, Feng, X, Zoecklein, L, Fu, YX & Roos, RP 2003, 'Membrane lymphotoxin is required for resistance to Theiler's virus infection', International Immunology, vol. 15, no. 8, pp. 955-962. https://doi.org/10.1093/intimm/mcg094

Membrane lymphotoxin is required for resistance to Theiler's virus infection. / Lin, Xiaoqi; Ma, Xiaoxing; Rodriguez, Moses; Feng, Xuan; Zoecklein, Laurie; Fu, Yang Xin; Roos, Raymond P.

In: International Immunology, Vol. 15, No. 8, 01.08.2003, p. 955-962.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Membrane lymphotoxin is required for resistance to Theiler's virus infection

AU - Lin, Xiaoqi

AU - Ma, Xiaoxing

AU - Rodriguez, Moses

AU - Feng, Xuan

AU - Zoecklein, Laurie

AU - Fu, Yang Xin

AU - Roos, Raymond P.

PY - 2003/8/1

Y1 - 2003/8/1

N2 - Lymphotoxin (LT) and tumor necrosis factor (TNF) are important in immune system development and function. LT consists of soluble LT-α3, which binds to TNF-R1 and TNF-R2, and membrane LT-α1β2, which binds to LT-β-R. We investigated the role of LT and TNF in disease induced by Daniel's (DA) strain of Theiler's murine encephalomyelitis virus (TMEV) since the immune response is believed to be important in both resistance to DA infection as well as mediation of virus-induced demyelination. DA persisted and induced inflammatory demyelination in LT-α-/- (but not TNF-/-) weanling mice of a normally resistant haplotype (C57BL/6), suggesting that LT, but not TNF, is critical for resistance to DA infection. This activity of LT depends on membrane LT-α1β2 and not soluble LT-α3, since DA virus persisted and induced inflammatory demyelination in LT-β-R-/-, but not TNF-R1-/- or TNF-R2-/-, mice. The LT-α-/- and LT-β-R-/- mice failed to mount a virus-specific cytotoxic T cell response. Treatment of weanling C57BL/6 mice with LT-β-R-lg, which blocks membrane LT activity, failed to increase susceptibility, suggesting that the LT effect is related to its action on immune system development which is fixed by 3 weeks of age. Our data suggest that membrane LT is important in resistance to DA infection (possibly through interference with CD8+ T cell development and function). There was relatively little demyelination associated with inflammation in LT-α-/- and LT-β-R-/- mice compared to susceptible SJL mice, suggesting the possibility that LT plays a role in mediating demyelination.

AB - Lymphotoxin (LT) and tumor necrosis factor (TNF) are important in immune system development and function. LT consists of soluble LT-α3, which binds to TNF-R1 and TNF-R2, and membrane LT-α1β2, which binds to LT-β-R. We investigated the role of LT and TNF in disease induced by Daniel's (DA) strain of Theiler's murine encephalomyelitis virus (TMEV) since the immune response is believed to be important in both resistance to DA infection as well as mediation of virus-induced demyelination. DA persisted and induced inflammatory demyelination in LT-α-/- (but not TNF-/-) weanling mice of a normally resistant haplotype (C57BL/6), suggesting that LT, but not TNF, is critical for resistance to DA infection. This activity of LT depends on membrane LT-α1β2 and not soluble LT-α3, since DA virus persisted and induced inflammatory demyelination in LT-β-R-/-, but not TNF-R1-/- or TNF-R2-/-, mice. The LT-α-/- and LT-β-R-/- mice failed to mount a virus-specific cytotoxic T cell response. Treatment of weanling C57BL/6 mice with LT-β-R-lg, which blocks membrane LT activity, failed to increase susceptibility, suggesting that the LT effect is related to its action on immune system development which is fixed by 3 weeks of age. Our data suggest that membrane LT is important in resistance to DA infection (possibly through interference with CD8+ T cell development and function). There was relatively little demyelination associated with inflammation in LT-α-/- and LT-β-R-/- mice compared to susceptible SJL mice, suggesting the possibility that LT plays a role in mediating demyelination.

KW - Cytokine

KW - Cytotoxic T lymphocyte

KW - Demyelination

KW - Lymphotoxin

KW - Theiler's virus

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U2 - 10.1093/intimm/mcg094

DO - 10.1093/intimm/mcg094

M3 - Review article

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VL - 15

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