Related Experiment Videos
Sonic hedgehog promotes cell cycle progression in activated peripheral CD4(+) T lymphocytes
Jacqueline A Lowrey1, Gareth A Stewart, Susannah Lindey
1Immunobiology Group, Medical Research Council Center for Inflammation Research, University of Edinburgh Medical School, Edinburgh, United Kingdom. J.A.Lowrey@ed.ac.uk
Journal of Immunology (Baltimore, Md. : 1950)
|August 8, 2002
Summary
Sonic hedgehog (Shh) signaling promotes CD4(+) T cell proliferation by advancing cell cycle progression. Endogenous Shh plays a physiological role, while exogenous Shh enhances T cell clonal expansion.
Area of Science:
- Immunology
- Developmental Biology
- Cell Signaling
Background:
- Sonic hedgehog (Shh) signaling is crucial for cell growth and differentiation.
- Recent studies suggest Shh's involvement in T cell development within the thymus.
- The role of Shh in peripheral T cell expansion remained unexplored.
Purpose of the Study:
- To investigate the contribution of Sonic hedgehog (Shh) signaling to the clonal expansion of peripheral CD4(+) T cells.
- To determine if Shh pathway components are expressed in peripheral CD4(+) T cells.
- To elucidate the mechanism by which Shh influences T cell proliferation.
Main Methods:
- Detection of Shh pathway components (Shh, patched, smoothened, Gli1) in peripheral CD4(+) T cells.
- Treatment of activated CD4(+) T cells with exogenous Shh peptide and neutralizing anti-Shh antibodies.
- Cell cycle analysis (S-G2 phase transition) and apoptosis assays.
- Quantitative mRNA analysis of Shh, Gli1, and bcl-2 in activated T cells.
Main Results:
- Shh and its pathway components are expressed in peripheral CD4(+) T cells.
- Exogenous Shh significantly enhanced proliferation of activated CD4(+) T cells, independent of anti-apoptotic effects.
- Shh promotes T cell entry into the S-G2 proliferative phase.
- Neutralizing anti-Shh antibodies reduced T cell proliferation, indicating a role for endogenous Shh.
- Upregulation of Shh and Gli1 mRNA observed in activated T cells.
- Upregulation of bcl-2 was observed only in activated T cells treated with Shh.
Conclusions:
- Endogenously produced Shh plays a physiological role in sustaining normal CD4(+) T cell proliferation.
- Exogenously added Shh enhances CD4(+) T cell clonal expansion by promoting cell cycle progression.
- The Shh pathway is a potential target for modulating T cell responses.