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Anthrax lethal toxin blocks MAPK kinase-dependent IL-2 production in CD4+ T cells

Hui Fang1, Ruth Cordoba-Rodriguez, Carla S R Lankford

  • 1Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|April 9, 2005
PubMed

Insights

Anthrax lethal toxin (LT) inactivates crucial signaling proteins in human T cells, inhibiting their proliferation and IL-2 production. This discovery enables new human cell-based assays for LT activity and reveals immune evasion strategies.

Area of Science:

  • Immunology
  • Molecular Biology
  • Microbial Pathogenesis

Background:

  • Anthrax lethal toxin (LT) is a key virulence factor targeting host cell signaling.
  • Current anthrax LT assays lack human cell relevance.
  • LT's effect on human T cell function is not well understood.

Purpose of the Study:

  • To investigate the impact of anthrax LT on human T cell function.
  • To establish human cell-based assays for anthrax LT activity.
  • To elucidate mechanisms of immune evasion by Bacillus anthracis.

Main Methods:

  • Utilized Jurkat T cell line and primary human CD4+ T cells.
  • Assessed MAPKK cleavage and T cell signaling pathways.
  • Measured IL-2 production and T cell proliferation.
  • Employed a protease inhibitor to block LT activity.

Main Results:

  • Anthrax LT specifically cleaves and inactivates MAPKKs in Jurkat and primary CD4+ T cells.
  • LT inhibits IL-2 production and proliferation in response to T cell receptor stimulation.
  • Protease inhibition fully restored IL-2 production.
  • LT caused a 95% reduction in anti-CD3-induced T cell responses.

Conclusions:

  • Anthrax LT directly impairs human T cell function, crucial for immune response regulation.
  • These findings support the development of novel human cell-based bioassays for LT.
  • LT's inhibition of T cell responses represents a significant immune evasion mechanism for Bacillus anthracis.

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