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Interleukins and T Helper Cells

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Science  24 Mar 2000:
Vol. 287, Issue 5461, pp. 2117
DOI: 10.1126/science.287.5461.2117h

Differentiation of naive CD4+ T cells into the T helper type 1 (TH1) phenotype requires signaling by interleukin (IL)-12 through the IL-12 receptor (IL-12R) _2 chain and activation of the signal transducer and activator of transcription (STAT) 4. On the other hand, induction of the TH2 phenotype from naive CD4+ T cells requires IL-4 binding to the IL-4 receptor and activation of STAT6. A concomitant reduction of IL-12R _2 also is observed. When naive CD4+ T cells are treated simultaneously with IL-4 and IL-12, the IL-4 effects predominate and TH2 cells develop. Thus, it has been hypothesized that IL-4-dependent decreases in IL-12R _2 expression abolish IL-12 signaling and allow for differentiation into the TH2 phenotype. Nishikomori et al. find that IL-12R b2 transgenic CD4+ T cells differentiated into TH2 cells in the presence of IL-4, or IL-4 and IL-12. In addition, IL-12 treatment of TH2 cells expressing functional IL-12 receptors did not induce the conversion of these cells into the TH1 phenotype. Now, Szabo et al. report that the transcription factor T-bet can repress IL-4 and redirect TH2 cells into the TH1 lineage.—JN

J. Exp. Med.191, 847 (2000); Cell100, 655 (2000).

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