Expression of JAGGED1 in T-lymphocytes results in thymic involution by inducing apoptosis of thymic stromal epithelial cells

L. J. Beverly, J. M. Ascano, A. J. Capobianco

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Proper development of the thymus and differentiation of T-lymphocytes requires cell-cell interactions between the developing T-lymphocytes and the thymic epithelia. The Delta/Serrate/Lag-2 (DSL)/Notch signal-transduction pathway is known to govern cell fate decisions required for proper development through direct cell-cell interactions. The functional consequences of specific DSL/Notch interactions during the development of a complex organ, such as the thymus, have not been thoroughly elucidated, however. In order to examine the role of DSL proteins during thymus development and T-lymphocyte differentiation, we targeted expression of JAGGED1 in T-lymphocyte progenitors via the control of the proximal lck promoter. Here, we report that expression of JAGGED1 in T cells causes premature involution of the thymus by directing thymic epithelial cells to undergo an apoptotic program. Adoptive transfer of JAGGED1 transgenic bone marrow into non-transgenic mice revealed that JAGGED1 expression on T cells does not alter T-cell differentiation, but is directly responsible for involution of the thymus. We propose that the phenotype of the lck-JAGGED1 transgenic mice is a direct result of specific DSL/Notch interactions and improper cell-to-cell signaling.

Original languageEnglish (US)
Pages (from-to)476-486
Number of pages11
JournalGenes and Immunity
Volume7
Issue number6
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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