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Repression of hedgehog signal transduction in T-lineage cells increases TCR-induced activation and proliferation

  • Anna Furmanski
    ,
  • Nicola J. Rowbotham
    ,
  • Ariadne L. Hager-Theodorides
    ,
  • Susan Ross
    ,
  • Ekati Drakopoulou
    ,
  • Costas Koufaris
  • University College London
    ,
  • Imperial College London
Research Output: Contribution to journal Article Peer-review

Open access

Abstract

Hedgehog proteins signal for differentiation, survival and proliferation of the earliest thymocyte progenitors, but their functions at later stages of thymocyte development and in peripheral T-cell function are controversial. Here we show that repression of Hedgehog (Hh) pathway activation in T-lineage cells, by expression of a transgenic repressor form of Gli2 (Gli2DeltaC2), increased T-cell differentiation and activationin response to TCR signalling. Expression of the Gli2DeltaC2 transgene increased differentiation from CD4(+)CD8(+) to single positive thymocyte, and increased peripheral T cell populations. Gli2DeltaC2 T-cells were hyper-responsive to activation by ligation of CD3 and CD28: they expressed cell surface activation markers CD69 and CD25 more quickly, and proliferated more than wild-type T-cells. These data show that Hedgehog pathway activation in thymocytes and T-cells negatively regulates TCR-dependent differentiation and proliferation. Thus, as negative regulators of TCR-dependent events, Hh proteins provide an environmental influence on T-cell fate.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Journal (Volume, Issue Number)

Cell Cycle (Volume 7, Issue 7)

Publication milestones

  • Published - 16/04/2008

Publication status

Published - 16/04/2008

ISSN

1538-4101

External Publication IDs

  • handle.net: 10547/623404
  • Scopus: 42449087714

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