Linked Life Data

15517614

Source:http://linkedlifedata.com/resource/pubmed/id/15517614

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-12-1
pubmed:abstractText
Interactions between CD40 on APC and CD154 (CD40L) expressed by activated CD4(+) T cells are crucially involved in formation and function of germinal centers (GC), but mechanistic insight into these interactions remains limited. Functional studies have mostly been restricted to experimental immunization of young-adult inbred SPF rodents that are often genetically manipulated, while studies in humans disallow in vivo manipulation. Therefore, we asked whether a functional antagonist of CD40 interferes with natural GC formation in adult cynomolgus monkeys (Macaca fascicularis) exposed to the environmental antigens of their conventional housing in captivity. Animals were treated with different doses of a unique chimeric antagonist anti-CD40 mAb (ch5D12) and analyzed 1 week or 7 weeks after last injection. Detailed in situ analysis showed that high-dose anti-CD40 treatment increased the ratio of primary over secondary follicles compared to PBS or low-dose treatment, indicative of impairment of the CG reaction. This impairment was reversible since recovery animals, except those with residual anti-CD40 levels, had normalized ratios. Anti-CD40 treatment was associated with decreased antibody production and increased numbers of apoptotic cells in GC. These data demonstrate that CD40-CD154 interactions are pivotal in physiological GC formation in primates responding to environmental antigens, and they support immunotherapeutic strategies using antagonist anti-CD40.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3446-55
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Antagonist anti-human CD40 antibody inhibits germinal center formation in cynomolgus monkeys.
pubmed:affiliation
Department of Immunology, Erasmus MC - Rotterdam, Rotterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't