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

Lookup NU author(s): Professor Catharien Hilkens


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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.

Publication metadata

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

Publication type: Article

Publication status: Published

Journal: European Journal of Immunology

Year: 2001

Volume: 31

Issue: 4

Pages: 1055-1065

ISSN (print): 0014-2980

ISSN (electronic): 1521-4141

Publisher: Wiley - V C H Verlag GmbH & Co.


DOI: 10.1002/1521-4141(200104)31:4<1055::AID-IMMU1055>3.0.CO;2-7

Notes: 0014-2980 Journal Article


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