Linked Life Data

12097399

Source:http://linkedlifedata.com/resource/pubmed/id/12097399

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-7-4
pubmed:abstractText
Long-term resistance to Toxoplasma gondii is dependent on the development of parasite-specific T cells that produce IFN-gamma. CD28 is a costimulatory molecule important for optimal activation of T cells, but CD28(-/-) mice are resistant to T. gondii, demonstrating that CD28-independent mechanisms regulate T cell responses during toxoplasmosis. The identification of the B7-related protein 1/inducible costimulator protein (ICOS) pathway and its ability to regulate the production of IFN-gamma suggested that this pathway may be involved in the CD28-independent activation of T cells required for resistance to T. gondii. In support of this hypothesis, infection of wild-type or CD28(-/-) mice with T. gondii resulted in the increased expression of ICOS by activated CD4(+) and CD8(+) T cells. In addition, both costimulatory pathways contributed to the in vitro production of IFN-gamma by parasite-specific T cells and when both pathways were blocked, there was an additive effect that resulted in almost complete inhibition of IFN-gamma production. Although in vivo blockade of the ICOS costimulatory pathway did not result in the early mortality of wild-type mice infected with T. gondii, it did lead to increased susceptibility of CD28(-/-) mice to T. gondi associated with reduced serum levels of IFN-gamma, increased parasite burden, and increased mortality compared with the control group. Together, these results identify a critical role for ICOS in the protective Th1-type response required for resistance to T. gondii and suggest that ICOS and CD28 are parallel costimulatory pathways, either of which is sufficient to mediate resistance to this intracellular pathogen.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
169
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
937-43
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12097399-Animals, pubmed-meshheading:12097399-Antigens, CD28, pubmed-meshheading:12097399-Antigens, CD80, pubmed-meshheading:12097399-Antigens, Differentiation, T-Lymphocyte, pubmed-meshheading:12097399-Brain, pubmed-meshheading:12097399-Genetic Predisposition to Disease, pubmed-meshheading:12097399-Immune Sera, pubmed-meshheading:12097399-Immunity, Innate, pubmed-meshheading:12097399-Inducible T-Cell Co-Stimulator Ligand, pubmed-meshheading:12097399-Inducible T-Cell Co-Stimulator Protein, pubmed-meshheading:12097399-Interferon-gamma, pubmed-meshheading:12097399-Leukocytes, Mononuclear, pubmed-meshheading:12097399-Lymphocyte Activation, pubmed-meshheading:12097399-Mice, pubmed-meshheading:12097399-Mice, Inbred C57BL, pubmed-meshheading:12097399-Mice, Inbred CBA, pubmed-meshheading:12097399-Mice, Knockout, pubmed-meshheading:12097399-T-Lymphocyte Subsets, pubmed-meshheading:12097399-Toxoplasma, pubmed-meshheading:12097399-Toxoplasmosis, Animal
pubmed:year
2002
pubmed:articleTitle
A role for inducible costimulator protein in the CD28- independent mechanism of resistance to Toxoplasma gondii.
pubmed:affiliation
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't