Sonic hedgehog signaling modulates activation of and cytokine production by human peripheral CD4+ T cells
| Autor: | Susannah Lindey, Paul M. Fitch, Sonia J. Wakelin, Jacqueline A. Lowrey, Margaret J. Dallman, Sarah E. M. Howie, Gareth A. Stewart, Jonathan Robert Lamb |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Interleukin 2
Antigens Differentiation T-Lymphocyte CD4-Positive T-Lymphocytes Patched Receptors animal structures T cell Immunology Dose-Response Relationship Immunologic Receptors Cell Surface Lymphocyte Activation Interleukin 21 Interferon-gamma Adjuvants Immunologic Antigens CD medicine Immunology and Allergy Cytotoxic T cell Humans Hedgehog Proteins Lectins C-Type IL-2 receptor Sonic hedgehog Cells Cultured biology ZAP70 Immune Sera Membrane Proteins Receptors Interleukin-2 Molecular biology Hedgehog signaling pathway medicine.anatomical_structure embryonic structures biology.protein Trans-Activators Cytokines Interleukin-2 medicine.drug Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 169(10) |
| ISSN: | 0022-1767 |
| Popis: | Sonic hedgehog (Shh) is important in the growth and differentiation of a variety of cell types, including the development of T cells in the thymus. This prompted us to investigate whether Shh signaling is a functional component of the physiological response of human mature CD4+ T cells following Ag recognition. In this study, we demonstrate that Shh and its receptor Patched (Ptc) are expressed on resting and activated human peripheral CD4+ T cells. In approximately one-half of the randomly selected, anonymous blood donors tested, exposure of anti-CD3/28 Ab-activated CD4+ T cells to the biologically active N-terminal Shh peptide increased the transcription of ptc, thereby demonstrating that Shh signaling had occurred. Furthermore, the addition of exogenous Shh amplified the production of IL-2, IFN-γ, and IL-10 by activated CD4+ T cells. The synthesis of IL-2 and IFN-γ, but not IL-10, by CD4+ T cells was down-regulated by the addition of neutralizing anti-Shh Ab. Cell surface expression of CD25 and CD69 on activated T cells was up-regulated by exogenous Shh, whereas in the presence of the neutralizing anti-Shh Ab expression it was reduced. Collectively, our findings demonstrate that Shh-mediated signaling is a physiological component of T cell responses, which acts to modulate CD4+ T cell effector function. |
| Databáze: | OpenAIRE |
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