Linked Life Data

11745345

Source:http://linkedlifedata.com/resource/pubmed/id/11745345

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2001-12-17
pubmed:abstractText
Immunostimulatory DNA sequences (ISS, CpG motifs) potently stimulate Th1 and cytotoxic T lymphocyte (CTL) responses to antigens and have thus generated considerable interest due to their potential use in immunotherapeutics. An array of cytokines are produced in response to ISS exposure, but the relative importance of each of these mediators in the stimulation of innate and adaptive ISS-induced immunity has yet to be fully investigated. To address this issue, we measured immune responses in mice with targeted deletions of the ISS-induced genes encoding IL-12 (IL-12(-/-)), IFN-gamma (IFN-gamma(-/-)), the IFN-gamma receptor (IFN-gammaR(-/-)), and the IFN-alpha/beta receptor (IFN-alpha/betaR(-/-)) after immunization with ISS-containing oligodeoxynucleotides and model antigens. IL-12(-/-) and IFN-alpha/betaR(-/-) mice were compromised in their ability to develop a cross-primed CTL response, whereas IFN-gamma(-/-) and IFN-gammaR(-/-) mice were not. In addition, lymphocytes from immunized IFN-alpha/betaR(-/-) mice had defective IFN-gamma responses to antigen restimulation. Antigen nonspecific ISS-induced B cell proliferation was normal in the four deficient strains; however, innate IL-6 production was reduced in IFN-gamma(-/-) and IFN-gammaR(-/-) splenocytes and eliminated in IFN-alpha/betaR(-/-) cells. While IL-12 production was defective in only the IFN-gamma(-/-) splenocytes, innate natural killer cell IFN-gamma synthesis was virtually absent in the IL-12(-/-) and IFN-alpha/betaR(-/-) mice. Thus, while IFN-alpha/beta, IFN-gamma, and IL-12 each play important and distinct roles in the development of the innate and adaptive immune responses to ISS, IFN-alpha/beta is a particularly crucial and currently under-appreciated factor in this system.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3281-90
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Type I interferon is required to mount an adaptive response to immunostimulatory DNA.
pubmed:affiliation
Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla 92093-0663, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't