Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-2-16
pubmed:abstractText
The CD28/CTLA-4 costimulatory signal is required for TCR-mediated T cell activation resulting in increased IL-2 production in vitro, but its role in IL-4 production is unclear and few studies have examined the function of CTLA-4/CD28 in the in vivo immune response. We have examined the in vivo effects of blocking the interaction of B7 with its ligands, CTLA-4 and CD28, in an IL-4 dominant in vivo immune response to goat anti-mouse IgD. This response is characterized by elevations in serum Igs preceded by elevations in IL-2 and the Th2 cytokines: IL-4, IL-9, and IL-10. The fusion protein CTLA4-Ig administered during the in vivo immune response to goat anti-mouse IgD caused an inhibition in elevations of IL-2, IL-4, and IL-9 gene expression at both day 3 and day 6 after immunization. In contrast, IL-10 cytokine gene expression as late as day 6 after immunization was not decreased. Cell sorting analysis demonstrated that TCR-alpha beta +, CD4+ T cells were the primary source of the elevated IL-10, suggesting that T cell activation leading to IL-10 gene expression may not require CTLA-4 ligand interactions. Similarly CTLA4-Ig completely blocked elevations in the number of IL-4- but not IL-10-secreting cells, as measured by ELISPOT, in both unsorted splenic cells and sorted CD4+, TCR-alpha beta+ T cells. In situ staining of spleen sections also showed inhibition of IL-4-producing cells. These results suggest that, with the notable exception of IL-10, interaction, of B7 with its ligands is required for elevated Th2 cytokine gene expression and secretion during a primary systemic IL-4-dominant response.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
154
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1078-87
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:7822784-Animals, pubmed-meshheading:7822784-Antigens, CD, pubmed-meshheading:7822784-Antigens, Differentiation, pubmed-meshheading:7822784-CTLA-4 Antigen, pubmed-meshheading:7822784-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:7822784-Female, pubmed-meshheading:7822784-Gene Expression Regulation, pubmed-meshheading:7822784-Immunity, pubmed-meshheading:7822784-Immunoconjugates, pubmed-meshheading:7822784-Immunoglobulin D, pubmed-meshheading:7822784-Immunohistochemistry, pubmed-meshheading:7822784-Interleukin-10, pubmed-meshheading:7822784-Interleukin-4, pubmed-meshheading:7822784-Lymphocyte Activation, pubmed-meshheading:7822784-Mice, pubmed-meshheading:7822784-Mice, Inbred BALB C, pubmed-meshheading:7822784-Receptors, Interleukin-2, pubmed-meshheading:7822784-Th2 Cells
pubmed:year
1995
pubmed:articleTitle
Requirement of CTLA-4 counter receptors for IL-4 but not IL-10 elevations during a primary systemic in vivo immune response.
pubmed:affiliation
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't