Publication:

IL-12-induced reversal of human Th2 cells is accompanied by full restoration of IL-12 responsiveness and loss of GATA-3 expression (2001)

Author(s): Smits HH, van Rietschoten JG, Hilkens CM, Sayilir R, Stiekema F, Kapsenberg ML, Wierenga EA

  • : IL-12-induced reversal of human Th2 cells is accompanied by full restoration of IL-12 responsiveness and loss of GATA-3 expression

Abstract: IL-12 is a potent inducer of IFN-gamma production and drives the development of Th1 cells. Human polarized Th2 cells do not express the signaling beta2-subunit of the IL-12R and, therefore, do not signal in response to IL-12. The question was raised as to what extent the loss of the IL-12Rbeta2 chain in Th2 cells has bearing on the stability of the human Th2 phenotype. In the present report, we show that restimulation of human fully polarized Th2 cells in the presence of IL-12 primes for a shift towards Th0/Th1 phenotypes, accompanied by suppression of GATA-3 expression and induction of T-bet expression. These reversed cells are further characterized by a marked IL-12Rbeta2 chain expression and fully restored IL-12-inducible STAT4 activation. The IL-12-induced phenotypic shift proved to be stable as a subsequent restimulation in the presence of IL-4 and in the absence of IL-12 could not undo the accomplished changes. Identical results were obtained with cells from atopic patients, both with polyclonal Th2 cell lines and allergen-specific Th2 cell clones. These findings suggest the possibility of restoring IL-12 responsiveness in established Th2 cells of atopic patients by stimulation in the presence of IL-12, and that IL-12-promoting immunotherapy can be beneficial for Th2-mediated immune disorders, targeting both naive and memory effector T cells.

Notes: 0014-2980 Journal Article

  • Short Title: IL-12-induced reversal of human Th2 cells is accompanied by full restoration of IL-12 responsiveness and loss of GATA-3 expression
  • Date: 21-03-2001
  • Journal: European Journal of Immunology
  • Volume: 31
  • Issue: 4
  • Pages: 1055-1065
  • Publisher: Wiley - V C H Verlag GmbH & Co.
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Allergens/immunology Antibodies, Monoclonal Cell Differentiation/drug effects Cells, Cultured Clone Cells/drug effects/immunology/metabolism DNA-Binding Proteins/genetics/*metabolism Flow Cytometry Gene Expression Regulation/drug effects Human Hypersensitivity/immunology Immunohistochemistry Immunotherapy Interferon Type II/immunology/metabolism Interleukin-12/immunology/*pharmacology Interleukin-4/immunology/metabolism/pharmacology Lymphocyte Activation Phenotype RNA, Messenger/genetics/metabolism Receptors, Interleukin/metabolism Signal Transduction/drug effects Support, Non-U.S. Gov't Th1 Cells/drug effects/immunology/metabolism Th2 Cells/*drug effects/immunology/*metabolism Trans-Activators/genetics/*metabolism Transcription Factors/genetics

Staff

Dr Catharien Hilkens
Reader in Immunotherapy