Linked Life Data

12370347

Source:http://linkedlifedata.com/resource/pubmed/id/12370347

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-10-8
pubmed:abstractText
Previously we reported that TGF-beta has an important role in the generation and expansion of human "professional" CD4(+)CD25(+) regulatory T cells in the periphery that have a cytokine-independent mechanism of action. In this study we used low-dose staphylococcal enterotoxin to induce T cell-dependent Ab production. We report that TGF-beta induces activated CD4(+)CD25(-) T cells to become Th3 suppressor cells. While stimulating CD4(+) cells with TGF-beta modestly increased expression of CD25 and intracellular CTLA-4 in primary cultures, upon secondary stimulation without TGF-beta the total number and those expressing these markers dramatically increased. This expansion was due to both increased proliferation and protection of these cells from activation-induced apoptosis. Moreover, adding as few as 1% of these TGF-beta-primed CD4(+) T cells to fresh CD4(+) cells and B cells markedly suppressed IgG production. The inhibitory effect was mediated by TGF-beta and was also partially contact dependent. Increased TGF-beta production was associated with a decreased production of IFN-gamma and IL-10. Depletion studies revealed that the precursors of these TGF-beta-producing CD4(+) suppressor cells were CD25 negative. These studies provide evidence that CD4(+)CD25(+) regulatory cells in human blood consist of at least two subsets that have TGF-beta-dependent and independent mechanisms of action. TGF-beta has an essential role in the generation of both of these T suppressor cell subsets from peripheral T cells. The ability to induce CD4(+) and CD8(+) cells to become regulatory cells ex vivo has the potential to be useful in the treatment of autoimmune diseases and to prevent transplant rejection.
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
169
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4183-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12370347-Adult, pubmed-meshheading:12370347-CD4-Positive T-Lymphocytes, pubmed-meshheading:12370347-Cell Communication, pubmed-meshheading:12370347-Cells, Cultured, pubmed-meshheading:12370347-Culture Media, Conditioned, pubmed-meshheading:12370347-Cytokines, pubmed-meshheading:12370347-Enterotoxins, pubmed-meshheading:12370347-Humans, pubmed-meshheading:12370347-Immunoglobulin G, pubmed-meshheading:12370347-Immunophenotyping, pubmed-meshheading:12370347-Lymphocyte Activation, pubmed-meshheading:12370347-Receptors, Interleukin-2, pubmed-meshheading:12370347-Staphylococcus aureus, pubmed-meshheading:12370347-Stem Cells, pubmed-meshheading:12370347-Superantigens, pubmed-meshheading:12370347-T-Lymphocyte Subsets, pubmed-meshheading:12370347-T-Lymphocytes, Regulatory, pubmed-meshheading:12370347-Transforming Growth Factor beta
pubmed:year
2002
pubmed:articleTitle
Generation ex vivo of TGF-beta-producing regulatory T cells from CD4+CD25- precursors.
pubmed:affiliation
Division of Rheumatology and Immunology, Department of Medicine, Keck School of Medicine, University of Southern California, 2211 Zonal Avenue, Los Angeles, CA 90033, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't