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International Immunology Advance Access published online on September 27, 2006
International Immunology, doi:10.1093/intimm/dxl096
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received December 29, 2005
Accepted September 2, 2006

Article

Sonic hedgehog promotes CD4+ T lymphocyte proliferation and modulates the expression of a subset of CD28-targeted genes

Vera S. F. Chan 1, Suk-yi Chau 1, Lina Tian 2, Yan Chen 1, Simon K. Y. Kwong 3, John Quackenbush 3, Margaret Dallman 4, Jonathan Lamb 5, and Paul K. H. Tam 1 *

1 Department of Surgery, University of Hong Kong Medical Centre, K-15 Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China
2 Department of Surgery, University of Hong Kong Medical Centre, K-15 Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China; Department of Surgery, Centre Clinical School, Faculty of Medicine, University of Sydney, Australia
3 Institute for Genome Research, Rockville, MD, USA
4 Department of Biological Sciences, Imperial College London, London SW7 2AZ, UK
5 Translational Medicine and Genetics, Clinical Pharmacology and Discovery Medicine, Room 5 1 23, GlaxoSmithKline, 891-995 Greenford Road, Greenford, Middlesex UB6 0HE, UK

* To whom correspondence should be addressed.
Paul K. H. Tam, E-mail: paultam{at}hkucc.hku.hk


  Abstract

Sonic hedgehog (Shh) is a crucial morphogen in the development of numerous tissues and organs, including the nervous system, gastrointestinal tract and lung. Recent findings suggest that Shh plays an important role in thymocyte development and peripheral T cell function. Here we report that the Shh receptors, patched and smoothened, are expressed in resting and activated T cells and their expression is regulated upon T cell activation. Shh protein is also detected on the surface of freshly isolated T cells. Although exogenous Shh alone does not activate resting T cells, it exhibits co-stimulatory activity which is reflected in its ability to potentiate CD3-mediated proliferation and cytokine production by CD4+ T cells. The co-stimulatory effect is most prominent at sub-optimal TCR stimulation level. Gene expression analysis reveals that Shh signaling in CD4+ T cells modulates a different set of transcriptional targets from that in neuronal cells. Furthermore, Shh co-stimulation modulates the expression of a subset of CD28-responsive genes, including cyclin A and B cell translocation gene 2.

Keywords: co-stimulation; gene regulation; sonic hedgehog; T cells.
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