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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1996-12-31
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pubmed:abstractText |
The development of T cell immunity is required to clear a pulmonary Cryptococcus neoformans infection (via the recruitment and activation of inflammatory cells). The objective of our studies was to determine whether TNF-alpha is required during the afferent phase of the response. The levels of TNF-alpha mRNA and protein in the lungs increased following intratracheal inoculation of CBA/J mice with C. neoformans 52 and preceded the development of an inflammatory response in the lungs. Administration of neutralizing TNF-alpha-specific antiserum on days 0, 3, 6, and 9 reduced inflammatory cell recruitment by 80% on day 13, resulting in a 3-fold increase in lung C. neoformans CFU. The number of CD4+ T cells was decreased by 65%, the number of neutrophils was decreased by 84%, and the number of macrophages was decreased by >98%. Strikingly, a single dose of neutralizing anti-TNF-alpha serum was sufficient to prevent the development of protective cell-mediated immunity on day 35 if administered on day 0, but was ineffective if delayed until day 14. Day 0 anti-TNF-alpha-treated mice could not generate cryptococcus-specific delayed type hypersensitivity reactivity, clear the infection from their lungs (10(4)-fold increase in CFU), control dissemination to the spleen and brain (10(5)- and 10(6)-fold increases in CFU), or adoptively transfer cryptococcus-specific immunity (mononuclear cell recruitment into the lungs following intratracheal challenge or footpad delayed type hypersensitivity). Thus, the production of TNF-alpha during the afferent phase of the immune response against a pulmonary C. neoformans infection (before day 14) is critical for the development of protective T cell immunity in both the lungs and extrapulmonary sites.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
157
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4529-36
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8906831-Animals,
pubmed-meshheading:8906831-Cryptococcosis,
pubmed-meshheading:8906831-Cryptococcus neoformans,
pubmed-meshheading:8906831-Female,
pubmed-meshheading:8906831-Kinetics,
pubmed-meshheading:8906831-Lung Diseases, Fungal,
pubmed-meshheading:8906831-Mice,
pubmed-meshheading:8906831-Mice, Inbred CBA,
pubmed-meshheading:8906831-T-Lymphocytes,
pubmed-meshheading:8906831-Tumor Necrosis Factor-alpha
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pubmed:year |
1996
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pubmed:articleTitle |
Afferent phase production of TNF-alpha is required for the development of protective T cell immunity to Cryptococcus neoformans.
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pubmed:affiliation |
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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