Linked Life Data

17114431

Source:http://linkedlifedata.com/resource/pubmed/id/17114431

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-11-20
pubmed:abstractText
Immunological adjuvants activate innate immune cells for Ag presentation and elicitation of cytokines like IL-12 that promote T cell expansion and effector differentiation. An important but elusive aim for most immunization strategies is to produce memory T cells that provide durable immunity. Recent evidence demonstrates that the context of Ag presentation instructionally programs T cells for short- and long-term responses. However, the role and mechanisms by which cytokines like IL-12 condition CD8 T cells for long-term responses remain relatively uncharacterized. In this study, we show that brief exposure (20 h) of naive TCR-transgenic CD8 cells to IL-12 during Ag stimulation leads to transient phosphorylation of STAT4 for robust effector differentiation. Moreover, the IL-12-induced STAT4 engenders greater clonal expansion of the Ag-activated CD8 cells by regulating the expression of the transcriptional factor Bcl3- and Bcl2-related genes that promote survival of Ag-activated CD8 cells. Remarkably, the IL-12-conditioned CD8 T cells demonstrate increased sensitivity to IL-7 and IL-15, whereby they are rendered "fit" for homeostatic self-renewal as well as augmented CD4-dependent recall responses that are effective at controlling Salmonella infection in vivo. This information provides new insights into mechanisms by which IL-12 conditions CD8 T cells for long-term immunity, which is likely to benefit development of new strategies for the use of IL-12 in infectious diseases and cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
177
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7618-25
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17114431-Animals, pubmed-meshheading:17114431-Blotting, Western, pubmed-meshheading:17114431-CD8-Positive T-Lymphocytes, pubmed-meshheading:17114431-Cell Differentiation, pubmed-meshheading:17114431-Flow Cytometry, pubmed-meshheading:17114431-Gene Expression, pubmed-meshheading:17114431-Gene Expression Regulation, pubmed-meshheading:17114431-Immunologic Memory, pubmed-meshheading:17114431-Interleukin-1, pubmed-meshheading:17114431-Interleukin-15, pubmed-meshheading:17114431-Interleukin-7, pubmed-meshheading:17114431-Lymphocyte Activation, pubmed-meshheading:17114431-Mice, pubmed-meshheading:17114431-Mice, Inbred C57BL, pubmed-meshheading:17114431-Mice, Transgenic, pubmed-meshheading:17114431-Phosphorylation, pubmed-meshheading:17114431-Proto-Oncogene Proteins, pubmed-meshheading:17114431-Receptors, Antigen, T-Cell, pubmed-meshheading:17114431-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17114431-STAT4 Transcription Factor, pubmed-meshheading:17114431-Transcription Factors
pubmed:year
2006
pubmed:articleTitle
IL-12-programmed long-term CD8+ T cell responses require STAT4.
pubmed:affiliation
Department of Immunology, Roswell Park Cancer Institute, 322 Cancer Cell Center, Elm and Carlton Streets, Buffalo, NY 14263, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural