Expression of lymphotoxin beta governs immunity at two distinct levels

Junt Tobias, Alexei V. Tumanov, Nicola Harris, Mathias Heikenwalder, Nicolas Zeller, Dmitry V. Kuprash, Adriano Aguzzi, Ludewig Burkhard, Sergei A. Nedospasov, Rolf M. Zinkernagel

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Interaction of lymphotoxin α1β2 (LTα1β2) with its receptor is key for the generation and maintenance of secondary lymphoid organ microstructure. We used mice conditionally deficient for LTβ on different lymphocyte subsets to determine how the LTβ-dependent lymphoid structure influences immune reactivity. All conditionally LTβ-deficient mice mounted normal immune responses against vesicular stomatitis virus (VSV), and were protected against lymphocytic choriomeningitis virus (LCMV). In contrast, they exhibited reduced immune responses against non-replicating antigens. Completely LTβ-deficient mice failed to retain VSV in the marginal zone and died from VSV infections, and they became virus carriers following infection with the non-cytopathic LCMV, which was correlated with defective virus replication in dendritic cells. It was ruled out that LTβ expression on lymphocytes influenced their activation, homing capacity, or maturation. We therefore conclude that LTβ expression influences immune reactivity at two distinct levels: (i) Expression of LTβ on lymphocytes enhances the induction of immune responses against limiting amounts of antigen. (ii) Expression of LTβ on non-lymphocytes governs antiviral immunity by enhancing antigen presentation on antigen-presenting cells. This prevents cytotoxic T lymphocytes exhaustion or death of the host by uncontrolled virus spread.

Original languageEnglish (US)
Pages (from-to)2061-2075
Number of pages15
JournalEuropean Journal of Immunology
Volume36
Issue number8
DOIs
StatePublished - Aug 2006
Externally publishedYes

Keywords

  • Antibody
  • Cytotoxic T lymphocyte
  • Lymphoid structure
  • Virus infections

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Tobias, J., Tumanov, A. V., Harris, N., Heikenwalder, M., Zeller, N., Kuprash, D. V., Aguzzi, A., Burkhard, L., Nedospasov, S. A., & Zinkernagel, R. M. (2006). Expression of lymphotoxin beta governs immunity at two distinct levels. European Journal of Immunology, 36(8), 2061-2075. https://doi.org/10.1002/eji.200626255