Linked Life Data

18424713

Source:http://linkedlifedata.com/resource/pubmed/id/18424713

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-4-21
pubmed:abstractText
IFN-gamma-producing CD8(+) T lymphocytes are essential effector cells that mediate protective immunity during murine toxoplasmosis, and yet their effector development remains poorly characterized. Vaccination with the carbamoyl phosphate synthase (CPS) mutant strain of Toxoplasma gondii was used to examine the CD8(+) T cell response in the peritoneal effector site. Four CTL subpopulations with varying effector potentials were defined based on the expression of effector molecules and the cell surface activation markers CD62L and killer cell lectin-like receptor G1 (KLRG1). Further phenotypic analysis revealed that the acquisition of KLRG1 among effector subpopulations correlated with the down-regulation of both IL-7R and CD27, suggesting that KLRG1 marks dominant, end-stage effector cells. Using gene-targeted mice, we tested the in vivo requirements of key IL-12 signaling components for effector CTL differentiation. Contrary to established models of viral and bacterial infection, CD8(+) T cell-intrinsic IL-12 signaling was required for the generation of IFN-gamma-producing CTLs in response to T. gondii. Importantly, the development of the KLRG1(+) effector subpopulations, but not the memory precursor-containing KLRG1(-) effector subset, was critically reliant on IL-12. Furthermore, IL-12 signaling-dependent T-bet expression was also found to be important for differentiation of KLRG1(+) effectors. Our results underscore a vital role for IL-12 in not only the induction of IFN-gamma expression but also in the development of heterogeneous subpopulations of effector CD8(+) T cells generated in response to the intracellular parasite T. gondii.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
180
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5935-45
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18424713-Animals, pubmed-meshheading:18424713-Antigens, CD27, pubmed-meshheading:18424713-CD8-Positive T-Lymphocytes, pubmed-meshheading:18424713-Carbon-Nitrogen Ligases, pubmed-meshheading:18424713-Cell Differentiation, pubmed-meshheading:18424713-Down-Regulation, pubmed-meshheading:18424713-Interferon-gamma, pubmed-meshheading:18424713-Interleukin-12, pubmed-meshheading:18424713-L-Selectin, pubmed-meshheading:18424713-Mice, pubmed-meshheading:18424713-Mice, Knockout, pubmed-meshheading:18424713-Mutation, pubmed-meshheading:18424713-Protozoan Proteins, pubmed-meshheading:18424713-Protozoan Vaccines, pubmed-meshheading:18424713-Receptors, Immunologic, pubmed-meshheading:18424713-Receptors, Interleukin-7, pubmed-meshheading:18424713-Signal Transduction, pubmed-meshheading:18424713-Toxoplasma, pubmed-meshheading:18424713-Toxoplasmosis, Animal
pubmed:year
2008
pubmed:articleTitle
IL-12 signaling drives CD8+ T cell IFN-gamma production and differentiation of KLRG1+ effector subpopulations during Toxoplasma gondii Infection.
pubmed:affiliation
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural