Sonic hedgehog signaling modulates activation of and cytokine production by human peripheral CD4+ T cells.

Autor: Stewart GA; Immunobiology Group, Medical Research Council Center for Inflammation Research, University of Edinburgh School of Medicine, Teviot Place, Edinburgh EH8 9AG, Scotland, United Kingdom., Lowrey JA, Wakelin SJ, Fitch PM, Lindey S, Dallman MJ, Lamb JR, Howie SE
Jazyk: angličtina
Zdroj: Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2002 Nov 15; Vol. 169 (10), pp. 5451-7.
DOI: 10.4049/jimmunol.169.10.5451
Abstrakt: 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.
Databáze: MEDLINE