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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.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Mar 15; Vol. 170 (6), pp. 3139-46. - Publication Year :
- 2003
-
Abstract
- 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.
- Subjects :
- Animals
Antigens, Protozoan pharmacology
CD4-Positive T-Lymphocytes pathology
Cell Division genetics
Cell Division immunology
Female
Genetic Predisposition to Disease
I-kappa B Proteins genetics
Immunity, Innate genetics
Interferon-gamma physiology
Killer Cells, Natural pathology
Lymphocyte Activation genetics
Lymphocyte Activation immunology
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
NF-KappaB Inhibitor alpha
NF-kappa B metabolism
Toxoplasma immunology
Toxoplasmosis, Animal genetics
Toxoplasmosis, Animal pathology
Transgenes immunology
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
Cytotoxicity, Immunologic genetics
Interferon-gamma biosynthesis
Killer Cells, Natural immunology
Killer Cells, Natural metabolism
NF-kappa B antagonists & inhibitors
Toxoplasmosis, Animal immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 170
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 12626571
- Full Text :
- https://doi.org/10.4049/jimmunol.170.6.3139