The Th1 life cycle: molecular control of IFN-γ to IL-10 switching

Trends Immunol. 2011 Jun;32(6):278-86. doi: 10.1016/ Epub 2011 Apr 30.


Control of IFN-γ-secreting T helper (Th) 1 cells prevents autoimmunity and immunopathology during infection. IL-10-mediated suppression of Th1 cells is achieved not only through IL-10 produced extrinsically, but also through a negative feedback loop that induces "intrinsic" IL-10 expression in cells also expressing IFN-γ, during Th1 lineage differentiation. Targeting this Th1 cell IFN-γ to IL-10 switching is a tantalising prospect for developing therapeutics for Th1-mediated diseases. In this review, the molecular pathways that regulate IFN-γ versus IL-10 expression in Th1 cells are examined, with focus on the role of complement regulator and T cell co-stimulatory molecule CD46, and also discussed are challenges and controversies in the field.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Proliferation
  • Humans
  • Interferon-gamma / immunology*
  • Interleukin-10 / immunology*
  • Interleukin-10 / metabolism
  • Signal Transduction
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism


  • Interleukin-10
  • Interferon-gamma