Sonic hedgehog promotes cell cycle progression in activated peripheral CD4(+) T lymphocytes
| Autor: | Susannah Lindey, Gerard F. Hoyne, Margaret J. Dallman, Gareth A. Stewart, Sarah E. M. Howie, Jonathan Robert Lamb, Jacqueline A. Lowrey |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Patched
CD4-Positive T-Lymphocytes Patched Receptors animal structures Lymphoid Tissue T cell Immunology Receptors Cell Surface Biology Lymphocyte Activation Zinc Finger Protein GLI1 Interleukin 21 Mice GLI1 Neutralization Tests medicine Immunology and Allergy Cytotoxic T cell Animals Hedgehog Proteins RNA Messenger Sonic hedgehog Oncogene Proteins Base Sequence Cell Cycle Intracellular Signaling Peptides and Proteins Membrane Proteins Cell cycle Molecular biology Peptide Fragments Cell biology Genes bcl-2 Up-Regulation Mice Inbred C57BL Kinetics medicine.anatomical_structure embryonic structures biology.protein Trans-Activators Smoothened Cell Division Signal Transduction Transcription Factors |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 169(4) |
| ISSN: | 0022-1767 |
| Popis: | Sonic hedgehog (Shh) signaling is important in the growth and differentiation of many cell types and recently has been reported to play a role in T cell development in the thymus. This prompted us to investigate whether or not Shh contributes to the clonal expansion of peripheral CD4+ T cells. In this study, we demonstrate that Shh and other components of the signaling pathway patched, smoothened, and Gli1 (glioma-associated oncogene) are expressed in peripheral CD4+ T cells. The addition of the biologically active amino-terminal Shh peptide had no effect on resting CD4+ T cells, but significantly enhanced proliferation of anti-CD3/28 Ab-activated CD4+ T cells. This was not due to antiapoptotic effects, but by promoting entry of T cells into the S-G2 proliferative phase of the cell cycle. Neutralizing anti-Shh Ab reduced T cell proliferation by inhibiting cell transition into the S-G2 phase, suggesting that endogenously produced Shh plays a physiological role in the clonal expansion of T cells. Furthermore, we have observed a significant up-regulation of Shh and Gli1 (glioma-associated oncogene) mRNA in activated CD4+ T cells with or without addition of exogenous Shh, which corresponds with maximal CD4+ T cell proliferation, whereas bcl-2 was only up-regulated in activated cells in the presence of Shh. Our findings suggest that endogenously produced Shh may play a role in sustaining normal CD4+ T cell proliferation and exogenously added Shh enhances this response. |
| Databáze: | OpenAIRE |
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