The Journal of Experimental Medicine
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Published online 6 March 2000.
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© The Rockefeller University Press, 0022-1007/2000/3/847/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 5, March 6, 2000 847-858

Original Article

T Helper Type 2 Cell Differentiation Occurs in the Presence of Interleukin 12 Receptor ß2 Chain Expression and Signaling

Ryuta Nishikomoria, Rolf O. Ehrhardtb, and Warren Strobera
a Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1890
b Protein Design Labs, Inc., Fremont, California 94555

Correspondence to: Warren Strober, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1890. Tel:301-496-6810 Fax:301-402-2240 E-mail:wstrober{at}niaid.nih.gov.

Released online: 6 March 2000

The differentiation of CD4+ T cells into T helper type 1 (Th1) cells is driven by interleukin (IL)-12 through the IL-12 receptor ß2 (IL-12Rß2) chain, whereas differentiation into Th2 cells is driven by IL-4, which downregulates IL-12Rß2 chain. We reexamined such differentiation using IL-12Rß2 chain transgenic mice. We found that CD4+ T cells from such mice were able to differentiate into Th2 cells when primed with IL-4 or IL-4 plus IL-12. In the latter case, the presence of IL-4 suppressed interferon (IFN)-{gamma} production 10–100-fold compared with cells cultured in IL-12 alone. Finally, in studies of the ability of IL-12 to convert Th2 cells bearing a competent IL-12R to the Th1 cells, we showed that: (a) T cells bearing the IL-12Rß2 chain transgene and primed under Th2 conditions could not be converted to Th1 cells by repeated restimulation under Th1 conditions; and (b) established Th2 clones transfected with the IL-12Rß2 chain construct continued to produce IL-4 when cultured with IL-12. These studies show that IL-4–driven Th2 differentiation can occur in the presence of persistent IL-12 signaling and that IL-4 inhibits IFN-{gamma} production under these circumstances. They also show that established Th2 cells cannot be converted to Th1 cells via IL-12 signaling.

Key Words: cytokine, interleukin 4, reversibility, signal transducer and activator of transcription 4, T helper type 1


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