Source:http://linkedlifedata.com/resource/pubmed/id/17237416
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2007-1-22
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pubmed:abstractText |
Previous work has shown that agonistic Abs to CD40 (anti-CD40) can boost weak CD8 T cell responses as well as substitute for CD4 T cell function during chronic gammaherpes virus infection. Agonistic anti-CD40 treatment has, therefore, been suggested as a potential therapeutic strategy in immunocompromised patients. In this study, we investigated whether agonistic anti-CD40 could substitute for CD4 T cell help in generating a sustained CD8 T cell response and prevent viral recrudescence following infection with lymphocytic choriomeningitis virus (LCMV). Contrary to expectations, we found that anti-CD40 treatment of MHC class II-deficient mice infected with a moderate dose of LCMV resulted in severe suppression of the antiviral CD8 T cell response and uncontrolled virus spread, rather than improved CD8 T cell immune surveillance. In Ab-treated wild-type mice, the antiviral CD8 T cell response also collapsed prematurely, and virus clearance was delayed. Additional analysis revealed that, following anti-CD40 treatment, the virus-specific CD8 T cells initially proliferated normally, but an increased cell loss compared with that in untreated mice was observed. The anti-CD40-induced abortion of virus-specific CD8 T cells during LCMV infection was IL-12 independent, but depended partly on Fas expression. Notably, similar anti-CD40 treatment of vesicular stomatitis virus-infected mice resulted in an improved antiviral CD8 T cell response, demonstrating that the effect of anti-CD40 treatment varies with the virus infection studied. For this reason, we recommend further evaluation of the safety of this regimen before being applied to human patients.
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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 |
Feb
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
178
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1662-70
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pubmed:meshHeading |
pubmed-meshheading:17237416-Animals,
pubmed-meshheading:17237416-Antibodies,
pubmed-meshheading:17237416-Antigens, CD40,
pubmed-meshheading:17237416-CD8-Positive T-Lymphocytes,
pubmed-meshheading:17237416-Histocompatibility Antigens Class II,
pubmed-meshheading:17237416-Immunity,
pubmed-meshheading:17237416-Immunosuppression,
pubmed-meshheading:17237416-Lymphocytic Choriomeningitis,
pubmed-meshheading:17237416-Lymphocytic choriomeningitis virus,
pubmed-meshheading:17237416-Mice,
pubmed-meshheading:17237416-Mice, Knockout
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pubmed:year |
2007
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pubmed:articleTitle |
Agonistic anti-CD40 antibody profoundly suppresses the immune response to infection with lymphocytic choriomeningitis virus.
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pubmed:affiliation |
Institute of Medical Microbiology, University of Copenhagen, Copenhagen, Denmark.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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