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

Gareth A Stewart, Jacqueline A Lowrey, Sonia J Wakelin, Paul M Fitch, Susannah Lindey, Margaret J Dallman, Jonathan R Lamb, Sarah E M Howie

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)5451-7
Number of pages7
JournalJournal of Immunology
Issue number10
Publication statusPublished - 15 Nov 2002


  • Adjuvants, Immunologic
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD4-Positive T-Lymphocytes
  • Cells, Cultured
  • Cytokines
  • Dose-Response Relationship, Immunologic
  • Hedgehog Proteins
  • Humans
  • Immune Sera
  • Interferon-gamma
  • Interleukin-2
  • Lectins, C-Type
  • Lymphocyte Activation
  • Membrane Proteins
  • Receptors, Cell Surface
  • Receptors, Interleukin-2
  • Signal Transduction
  • Trans-Activators


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