Linked Life Data

16210616

Source:http://linkedlifedata.com/resource/pubmed/id/16210616

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-10-7
pubmed:abstractText
CD8(+) T cells are crucial for host defense against invading pathogens and malignancies. However, relatively little is known about intracellular signaling events that control the genetic program of their activation and differentiation. Using CD8(+) T cells from TCR-transgenic mice crossed to protein kinase C-theta (PKCtheta)-deficient mice, we report that PKCtheta is not required for Ag-induced CD8(+) T cell proliferation, but is important for T cell survival and differentiation into functional, cytokine-producing CTLs. Ag-stimulated PKCtheta(-/-) T cells underwent accelerated apoptosis associated with deregulated expression of Bcl-2 family proteins and displayed reduced activation of ERKs and JNKs. Some defects in the function of PKCtheta(-/-) T cells (poor survival and reduced Bcl-2 and Bcl-x(L) expression, CTL activity, and IFN-gamma expression) were partially or fully restored by coculture with wild-type T cells or by addition of exogenous IL-2, whereas others (increased Bim(EL) expression and TNF-alpha production) were not. These findings indicate that PKCtheta, although not essential for initial Ag-induced proliferation, nevertheless plays an important role in promoting and extending T cell survival, thereby enabling the complete genetic program of effector CD8(+) differentiation. The requirement for PKCtheta in different types of T cell-dependent responses may, therefore, depend on the overall strength of signaling by the TCR and costimulatory receptors and may reflect, in addition to its previously established role in activation, an important, hitherto unappreciated, role in T cell survival.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5126-34
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16210616-Animals, pubmed-meshheading:16210616-Antigens, pubmed-meshheading:16210616-CD8-Positive T-Lymphocytes, pubmed-meshheading:16210616-Cell Differentiation, pubmed-meshheading:16210616-Cell Proliferation, pubmed-meshheading:16210616-Cell Survival, pubmed-meshheading:16210616-Cells, Cultured, pubmed-meshheading:16210616-Coculture Techniques, pubmed-meshheading:16210616-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:16210616-Isoenzymes, pubmed-meshheading:16210616-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:16210616-Mice, pubmed-meshheading:16210616-Mice, Inbred C57BL, pubmed-meshheading:16210616-Mice, Knockout, pubmed-meshheading:16210616-Mice, Transgenic, pubmed-meshheading:16210616-Protein Kinase C, pubmed-meshheading:16210616-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:16210616-Transduction, Genetic, pubmed-meshheading:16210616-bcl-X Protein
pubmed:year
2005
pubmed:articleTitle
Protein kinase C-theta is an early survival factor required for differentiation of effector CD8+ T cells.
pubmed:affiliation
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural