T Helper Type 2 Cell Differentiation Occurs in the Presence of Interleukin 12 Receptor β2 Chain Expression and Signaling

Ryuta Nishikomori^a, Rolf O. Ehrhardt^b, , and Warren Strober^a

^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
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1890.301-402-2240301-496-6810

wstrober{at}niaid.nih.gov

Abstract: The differentiation of CD4⁺ T cells into T helper type 1 (Th1) cells is driven by interleukin (IL)-12 through the IL-12 receptor β2 (IL-12Rβ2) chain, whereas differentiation into Th2 cells is driven by IL-4, which downregulates IL-12Rβ2 chain. We reexamined such differentiation using IL-12Rβ2 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)- 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-12Rβ2 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-12Rβ2 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- 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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