Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation

Nicola J. Rowbotham; Ariadne L. Hager-Theodorides; Ekati Drakopoulou; Julian Dyson; Susan V. Outram; Tessa Crompton; Marek Cebecauer; Divya K. Shah

doi:10.1182/blood-2006-07-037655

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Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation

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Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation

Nicola J. Rowbotham, Ariadne L. Hager-Theodorides, Ekati Drakopoulou, Julian Dyson, Susan V. Outram, Tessa Crompton, Marek Cebecauer and Divya K. Shah

Blood, Vol.109(9), pp.3757-3766

05/01/2007

DOI: 10.1182/blood-2006-07-037655

PMCID: PMC1874579

PMID: 17227833

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Abstract

TCR signal strength is involved in many cell fate decisions in the T-cell lineage. Here, we show that transcriptional events induced by Hedgehog (Hh) signaling reduced TCR signal strength in mice. Activation of Hh signaling in thymocytes in vivo by expression of a transgenic transcriptional-activator form of Gli2 (Gli2DeltaN(2)) changed the outcome of TCR ligation at many stages of thymocyte development, allowing self-reactive cells to escape clonal deletion; reducing transgenic TCR-mediated positive selection; reducing the ratio of CD4/CD8 single-positive (SP) cells; and reducing cell surface CD5 expression. In contrast, in the Shh(-/-) thymus the ratio of CD4/CD8 cells and both positive and negative selection of a transgenic TCR were increased, demonstrating that Shh does indeed influence TCR repertoire selection and the transition from double-positive (DP) to SP cell in a physiological situation. In peripheral T cells, Gli2DeltaN(2) expression attenuated T-cell activation and proliferation, by a mechanism upstream of ERK phosphorylation.

Obstetrics and Gynecology

Details

Title: Subtitle: Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation
Creators: Nicola J. Rowbotham
Ariadne L. Hager-Theodorides
Ekati Drakopoulou
Julian Dyson
Susan V. Outram
Tessa Crompton
Marek Cebecauer
Divya K. Shah - University of Iowa
Resource Type: Journal article
Publication Details: Blood, Vol.109(9), pp.3757-3766
DOI: 10.1182/blood-2006-07-037655
PMID: 17227833
PMCID: PMC1874579
NLM abbreviation: Blood
ISSN: 0006-4971
Language: English
Date published: 05/01/2007
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983557244702771

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