Inhibition of NF-κB activity in T and NK cells results in defective effector cell expansion and production of IFN-γ required for resistance to Toxoplasma gondii

Cristina M. Tato, Alejandro Villarino, Jorge H. Caamaño, Mark Boothby, Christopher A. Hunter

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

To define the role of NF-κB in the development of T cell responses required for resistance to Toxoplasma gondii, mice in which T cells are transgenic for a degradation-resistant (ΔN) form of IκBα, an inhibitor of NF-κB, were challenged with T. gondii and their response to infection compared with control mice. IκBα(ΔN)-transgenic (Tg) mice succumbed to T. gondii infection between days 12 and 35, and death was associated with an increased parasite burden compared with wild-type (Wt) controls. Analysis of the responses of infected mice revealed that IL-12 responses were comparable between strains, but Tg mice had a marked reduction in systemic levels of IFN-γ, the major mediator of resistance to T. gondii. In addition, the infection-induced increase in NK cell activity observed in Wt mice was absent from Tg mice and this correlated with NK cell expression of the transgene. Infection-induced activation of CD4+ T cells was similar in Wt and Tg mice, but expansion of activated CD4+T cells was markedly reduced in the Tg mice. This difference in T cell numbers correlated with a reduced capacity of these cells to proliferate after stimulation and was associated with a major defect in the ability of CD4+ T cells from infected mice to produce IFN-γ. Together, these studies reveal that inhibition of NF-κB activity in T and NK cells results in defective effector cell expansion and production of IFN-γ required for resistance to T. gondii.

Original languageEnglish (US)
Pages (from-to)3139-3146
Number of pages8
JournalJournal of Immunology
Volume170
Issue number6
DOIs
StatePublished - Mar 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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