1. Sonic hedgehog signaling modulates activation of and cytokine production by human peripheral CD4+ T cells.
- Author
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Stewart GA, Lowrey JA, Wakelin SJ, Fitch PM, Lindey S, Dallman MJ, Lamb JR, and Howie SE
- Subjects
- Adjuvants, Immunologic blood, Adjuvants, Immunologic physiology, Antigens, CD biosynthesis, Antigens, CD metabolism, Antigens, Differentiation, T-Lymphocyte biosynthesis, Antigens, Differentiation, T-Lymphocyte metabolism, Cells, Cultured, Cytokines antagonists & inhibitors, Cytokines blood, Dose-Response Relationship, Immunologic, Hedgehog Proteins, Humans, Immune Sera pharmacology, Interferon-gamma antagonists & inhibitors, Interferon-gamma biosynthesis, Interleukin-2 antagonists & inhibitors, Interleukin-2 biosynthesis, Lectins, C-Type, Membrane Proteins blood, Membrane Proteins physiology, Patched Receptors, Receptors, Cell Surface, Receptors, Interleukin-2 biosynthesis, Receptors, Interleukin-2 metabolism, Trans-Activators blood, Trans-Activators immunology, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, Cytokines biosynthesis, Lymphocyte Activation immunology, Signal Transduction immunology, Trans-Activators physiology
- Abstract
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-gamma, and IL-10 by activated CD4(+) T cells. The synthesis of IL-2 and IFN-gamma, 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.
- Published
- 2002
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