Cell Differentiation

Interleukin-12 Receptor β2 Chain and TH2 Cells

Science's STKE  14 Mar 2000:
Vol. 2000, Issue 23, pp. tw2
DOI: 10.1126/stke.2000.23.tw2

Differentiation of naïve CD4+ T cells into the T helper type 1 (TH1) phenotype requires signaling by interleukin (IL)-12 through the IL-12 receptor β2 chain, and activation of the signal transducer and activator of transcription (STAT) 4. On the other hand, induction of the TH2 phenotype from naïve CD4+ T cells requires IL-4 binding of the functional IL-4 receptor and activation of STAT6. A concomitant reduction of IL-12Rβ2 is also observed. When naïve CD4+ T cells are treated simultaneously with both 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-12Rβ2 expression prevent IL-12 signals, and this allows for differentiation into the TH2 phenotype. However, it is not known what effect constitutive expression of the IL-12Rβ2 chain has on the development of TH2 cells. Nishikomori et al. found that IL-12Rβ2 transgenic CD4+ T cells differentiated into TH2 cells in the presence of IL-4, or IL-4 and IL-12. IL-12 treatment of TH2 cells expressing functional IL-12 receptors did not induce the conversion of these cells into the TH1 phenotype if the cells were pretreated under TH2 conditions. Additionally, the authors found that the IL-12 receptor-bearing TH2 cells continued to synthesize IL-4 even in the presence of IL-12 in the growth medium. Thus, TH2 cells are resistant to TH1 conversion, and decreased expression of IL-12Rβ2 is not necessary for the establishment of the TH2 phenotype.

Nishikomori, R., Ehrhardt, R.O., and Strober, W. (2000) T helper type 2 cell differentiation occurs in the presence of interleukin-12 receptor β2 chain expression and signaling. J. Exp. Med. 191: 847-858. [Abstract] [Full Text]