Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2000-6-8
pubmed:abstractText
Differentiation of immature CD4(+)CD8(+) thymocytes to mature CD4(+) or CD8(+) T cells is induced by positive selection and appears to involve calcineurin-dependent activation of NFAT, a family of transcription factors. NFATx is predominantly expressed in CD4(+)CD8(+) thymocytes, whereas NFATp and NFATc are expressed at much lower levels in the thymus than in mature T cells. However, how or when each NFAT member is involved in the differentiation pathway is unclear. Using an in vitro model system where isolated CD4(+)CD8(+) thymocytes can survive and differentiate into semi-mature CD4-lineage T cells, we suggest that low calcineurin activity sustained for approximately 20 h is required for cell survival and differentiation. Accordingly, the DNA binding activity of NFAT slowly increased during the stimulation of 20 h to induce the differentiation. NFATx significantly contributed to the early rise, but the late increase was mostly due to NFATc activation. Meanwhile, the expression of NFATx mRNA decreased and that of NFATc mRNA increased. The DNA-binding activity of NFATp was detectable but low throughout the stimulation. NFATp became dominantly active after the semi-mature T cells differentiated into mature and activated CD4 T cells. These findings suggest that NFATx and NFATc successively play roles in T cell development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14708-16
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10799559-Animals, pubmed-meshheading:10799559-Base Sequence, pubmed-meshheading:10799559-CD4-Positive T-Lymphocytes, pubmed-meshheading:10799559-CD8-Positive T-Lymphocytes, pubmed-meshheading:10799559-Calcium Signaling, pubmed-meshheading:10799559-Cell Differentiation, pubmed-meshheading:10799559-DNA, pubmed-meshheading:10799559-DNA Primers, pubmed-meshheading:10799559-DNA-Binding Proteins, pubmed-meshheading:10799559-Humans, pubmed-meshheading:10799559-Mice, pubmed-meshheading:10799559-Mice, Transgenic, pubmed-meshheading:10799559-NFATC Transcription Factors, pubmed-meshheading:10799559-Nuclear Proteins, pubmed-meshheading:10799559-Receptors, Antigen, T-Cell, alpha-beta, pubmed-meshheading:10799559-Sirolimus, pubmed-meshheading:10799559-Tacrolimus, pubmed-meshheading:10799559-Thymus Gland, pubmed-meshheading:10799559-Transcription Factors
pubmed:year
2000
pubmed:articleTitle
Successive expression and activation of NFAT family members during thymocyte differentiation.
pubmed:affiliation
Integrative Projects, Mitsubishi Kasei Institute of Life Sciences, Machida-shi, Tokyo 194-8511, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't