Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2000-11-21
pubmed:abstractText
The NF-kappaB family of transcription factors are involved in the regulation of innate and adaptive immune functions associated with resistance to infection. To assess the role of NF-kappaB(2) in the regulation of cell-mediated immunity, mice deficient in the NF-kappaB(2) gene (NF-kappaB(2)(-/-)) were challenged with the intracellular parasite Toxoplasma gondii. Resistance to this opportunistic pathogen is dependent on the production of IL-12, which is required for the development of innate NK cell and adaptive T cell responses dominated by the production of IFN-gamma necessary to control replication of this parasite. Although wild-type controls were resistant to T. gondii, NF-kappaB(2)(-/-) mice developed severe toxoplasmic encephalitis and succumbed to disease between 3 and 10 wk following infection. However, NF-kappaB(2) was not required for the ability of macrophages to produce IL-12 or to inhibit parasite replication and during the acute stage of infection, NF-kappaB(2)(-/-) mice had no defect in their ability to produce IL-12 or IFN-gamma and infection-induced NK cell responses appeared normal. In contrast, during the chronic phase of the infection, susceptibility of NF-kappaB(2)(-/-) mice to toxoplasmic encephalitis was associated with a reduced capacity of their splenocytes to produce IFN-gamma associated with a loss of CD4(+) and CD8(+) T cells. This loss of T cells correlated with increased levels of apoptosis and with elevated expression of the pro-apoptotic molecule Fas by T cells from infected NF-kappaB(2)(-/-) mice. Together, these results suggest a role for NF-kappaB(2) in the regulation of lymphocyte apoptosis and a unique role for this transcription factor in maintenance of T cell responses required for long-term resistance to T. gondii.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
165
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5720-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11067930-Animals, pubmed-meshheading:11067930-Antigens, CD95, pubmed-meshheading:11067930-Apoptosis, pubmed-meshheading:11067930-Chronic Disease, pubmed-meshheading:11067930-Cytotoxicity, Immunologic, pubmed-meshheading:11067930-Encephalitis, pubmed-meshheading:11067930-Female, pubmed-meshheading:11067930-Immunity, Cellular, pubmed-meshheading:11067930-Interferon-gamma, pubmed-meshheading:11067930-Interleukin-12, pubmed-meshheading:11067930-Killer Cells, Natural, pubmed-meshheading:11067930-Lymphocyte Activation, pubmed-meshheading:11067930-Macrophages, pubmed-meshheading:11067930-Male, pubmed-meshheading:11067930-Mice, pubmed-meshheading:11067930-Mice, Inbred C57BL, pubmed-meshheading:11067930-Mice, Inbred CBA, pubmed-meshheading:11067930-Mice, Knockout, pubmed-meshheading:11067930-NF-kappa B, pubmed-meshheading:11067930-NF-kappa B p52 Subunit, pubmed-meshheading:11067930-T-Lymphocytes, pubmed-meshheading:11067930-Toxoplasma, pubmed-meshheading:11067930-Toxoplasmosis, Animal, pubmed-meshheading:11067930-Toxoplasmosis, Cerebral
pubmed:year
2000
pubmed:articleTitle
Identification of a role for NF-kappa B2 in the regulation of apoptosis and in maintenance of T cell-mediated immunity to Toxoplasma gondii.
pubmed:affiliation
Medical Research Council Centre for Immune Regulation, School of Medicine, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't