Induction of Human T Helper Cell Type 1 Differentiation Results in Loss of IFN-γ Receptor β-Chain Expression

Hervé Groux, Thierry Sornasse, Françoise Cottrez, Jan E. De Vries, Robert L. Coffman, Maria Grazia Roncarolo, Hans Yssel

Research output: Contribution to journalArticlepeer-review

Abstract

Differential expression of cytokine receptors accounts for an important regulatory mechanism in differentiation of Th1/Th2 subsets. Here, we report that human Th0 and Th2 clones constitutively express transcripts for the IFN-γR β-chain, whereas mRNA for this signaling component of the IFN-γ receptor is absent in Th1 clones. Activation of T cell clones, however, resulted in a transient induction or enhancement of IFN-γR β-chain mRNA expression in Th1 clones and Th0/Th2 clones, respectively. IL-12-mediated Th1 cell differentiation of naive CD4+, CD45RA+ cord blood T cells, which constitutively express IFN-γR β-chain mRNA, resulted in a loss of expression of this cytokine receptor chain after 6 to 12 days of culture. In contrast, Th2 populations, differentiated from CD4+, CD45RA+ cord blood T cells in the presence of IL-4, continued to express high levels of IFN-γR β-chain transcripts. The loss of IFN-γR β-chain expression in Th1 populations was accompanied by a failure of IFN-γ to induce the expression of the IFN-γ-inducible gene, IFN response factor-1, whereas IFN-γ was effective in inducing IFN response factor-1 mRNA expression in Th0 and Th2 cells. These results indicate that down-regulation of the IFN-γR β-chain correlates with impaired IFN-γ-induced signaling in Th1 cells. Finally, Th2 populations, generated in the presence of both IL-4 and IFN-γ, expressed levels of IFN-γR β-chain transcripts similar to those produced by cells differentiated in the presence of IL-4 only, demonstrating that IFN-γ does not modulate the expression of its receptor. Together, these data indicate that human Th0/Th2 and Th1 subsets, respectively, can be distinguished based on the expression of the IFN-γR β-chain.

Original languageEnglish
Pages (from-to)5627-5631
Number of pages5
JournalJournal of Immunology
Volume158
Issue number12
Publication statusPublished - Jun 15 1997

ASJC Scopus subject areas

  • Immunology

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