音猬因子
细胞生物学
白细胞介素2受体
修补
T细胞
生物
细胞因子
受体
刺猬信号通路
信号转导
化学
分子生物学
免疫系统
免疫学
生物化学
作者
Gareth Stewart,Jacqueline A. Lowrey,Sonia J. Wakelin,Paul M. Fitch,Susannah Lindey,Margaret J. Dallman,Jonathan R. Lamb,Sarah Howie
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2002-11-15
卷期号:169 (10): 5451-5457
被引量:107
标识
DOI:10.4049/jimmunol.169.10.5451
摘要
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-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.
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