Early progression of thymocytes along the CD4/CD8 developmental pathway is regulated by a subset of thymic epithelial cells expressing transforming growth factor beta.
J Exp Med
; 179(5): 1495-506, 1994 May 01.
Article
en En
| MEDLINE
| ID: mdl-8163934
ABSTRACT
Precursor cells differentiate into mature CD4+ and CD8+ T cells in the inductive environment of the thymus by undergoing a series of distinct developmental steps marked by expression of the coreceptor molecules CD4 and CD8. Among the earliest cells to enter the CD4/CD8 developmental pathway are CD4-CD8lo precursors cells that differentiate into CD4+CD8+ thymocytes. Here we show that differentiation of precursor cells into CD4+CD8+ thymocytes requires at least one cell division and that their progression through a cell cycle is specifically retarded in the thymus by interaction with thymic epithelial cells that express transforming growth factor beta (TGF-beta) proteins. We also demonstrate that TGF-beta proteins, either in solution or bound to cell membranes, can regulate cell cycle progression and differentiation of CD4-CD8lo precursor cells into CD4+CD8+ thymocytes. The regulatory effect of TGF-beta is specific for CD4-CD8lo precursor cells as TGF-beta proteins do not regulate the earlier generation of CD4-CD8lo precursor cells from CD4-CD8- thymocytes. Finally, we demonstrate that TGF-beta proteins are expressed in vivo in the intact thymus on subcapsular and cortical thymic epithelium where they can contact developing CD4-CD8lo precursor cells. Thus, thymic epithelial cells expressing TGF-beta proteins can actively regulate the rate at which CD4+CD8+ thymocytes are generated from CD4-CD8lo precursor cells.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Timo
/
Antígenos CD4
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Subgrupos de Linfocitos T
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Factor de Crecimiento Transformador beta
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Antígenos CD8
Límite:
Animals
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Humans
Idioma:
En
Año:
1994
Tipo del documento:
Article