Linked Life Data

7682246

Source:http://linkedlifedata.com/resource/pubmed/id/7682246

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8 Pt 1
pubmed:dateCreated
1993-5-12
pubmed:abstractText
Abnormal development of T cells in the thymus is thought to be related to autoimmune disease and the expansion of the unusual CD4-CD8-B220+ peripheral T cel subset that results in lymphadenopathy in MRL-lpr/lpr mice. Although we and others have previously shown that rearranged TCR-transgenes alter T cell development in the thymus and abrogate lymphoproliferative disease in lpr mice, the origin and developmental pathway of the LN CD4-CD8-B220+ T cells has not been fully elucidated. We therefore undertook the systematic analysis of the effect of a TCR-beta transgene on the production and differentiation of (lymph node) LN T cells and the production, differentiation, and release of thymocyte T cell populations. In nontransgenic mice, there was increased proliferation of CD4-CD8-B220+ T cells in the LN of adult MRL-lpr/lpr mice compared to MRL(-)+/+ mice, as measured by in vivo BrdU labeling. These proliferating LN T cells were greatly reduced by thymectomy of adult MRL-lpr/lpr mice 1 wk before bromodeoxyuridine labeling, indicating that recent thymic emigrants or factors were required to sustain proliferation. In the thymus, there was increased production and accumulation of CD4+CD8+TCRdull thymocytes in nontransgenic MRL-lpr/lpr compared to MRL(-)+/+ mice. As the rate of maturation from CD4+CD8+TCRdull to CD4+CD8+TCRbright was the same (6%) in both MRL-lpr/lpr and MRL(-)+/+ mice, the accumulation of the immature population in the MRL-lpr/lpr mice could not be due to a maturation defect. However, there was a decrease in apoptosis and intrathymic death of CD4+CD8+TCRdull thymocytes in MRL-lpr/lpr compared to MRL(-)+/+ mice. Introduction of the TCR-beta transgene into lpr/lpr mice normalized the proliferation of T cells in the LN. In the thymus, the TCR-beta transgene resulted in a dramatic increase in maturation efficiency and a reduction in apoptosis in MRL(-)+/+ mice. These data suggest that the TCR transgene inhibits lymphoproliferation by reducing the production of "neglected" CD4+CD8+TCRdull thymocytes that will undergo Fas Ag-mediated apoptosis. They further suggest that in lpr mice, which express a mutated Fas Ag, the "neglected" thymocytes are able to continually escape to the periphery, where they proliferate.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
150
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3651-67
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Origin of CD4-CD8-B220+ T cells in MRL-lpr/lpr mice. Clues from a T cell receptor beta transgenic mouse.
pubmed:affiliation
Department of Medicine, University of Alabama, Birmingham.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.