Repression of hedgehog signal transduction in T-lineage cells increases TCR-induced activation and proliferation
AuthorsRowbotham, Nicola J.
Furmanski, Anna L.
Hager-Theodorides, Ariadne L.
Outram, Susan V.
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AbstractHedgehog 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.
CitationRowbotham NJ, Furmanski AL, Hager-Theodorides AL, Ross SE, Drakopoulou E, Koufaris C, Outram SV, Crompton T (2008) 'Repression of hedgehog signal transduction in T-lineage cells increases TCR-induced activation and proliferation', Cell Cycle, 7 (7), pp.-.
PublisherTaylor & Frances
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