Inhibition of NF-kappa B activity in T and NK cells results in defective effector cell expansion and production of IFN-gamma required for resistance to Toxoplasma gondii.

Tato CM, Villarino A, CaamaƱo JH, Boothby M, Hunter CA
J Immunol. 2003 170 (6): 3139-46

PMID: 12626571 · DOI:10.4049/jimmunol.170.6.3139

To define the role of NF-kappa B in the development of T cell responses required for resistance to Toxoplasma gondii, mice in which T cells are transgenic for a degradation-resistant (Delta N) form of I kappa B alpha, an inhibitor of NF-kappa B, were challenged with T. gondii and their response to infection compared with control mice. I kappa B alpha(Delta N)-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-gamma, 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-gamma. Together, these studies reveal that inhibition of NF-kappa B activity in T and NK cells results in defective effector cell expansion and production of IFN-gamma required for resistance to T. gondii.

MeSH Terms (22)

Animals Antigens, Protozoan CD4-Positive T-Lymphocytes Cell Division Cytotoxicity, Immunologic Female Genetic Predisposition to Disease I-kappa B Proteins Immunity, Innate Interferon-gamma Killer Cells, Natural Lymphocyte Activation Male Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Transgenic NF-kappa B NF-KappaB Inhibitor alpha Toxoplasma Toxoplasmosis, Animal Transgenes

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