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Responsiveness of Naive CD4 T Cells to Polarizing Cytokine Determines the Ratio of Th1 and Th2 Cell Differentiation
Biochemistry and Microbiology
  • Natallia Mikhalkevich
  • Brian Becknell
  • Michael A. Caligiuri
  • Michael D. Bates
  • Richard Harvey
  • Wei-ping Zeng, Marshall University
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The intrinsic features of naive CD4 T cells that affect their ability to respond to polarizing signals for Th cell differentiation are not well understood. In this study, we show that naive CD4 T cells from mice transgenic for the Hlx gene expressed lower levels of IL-4Rα. The down-regulation of IL-4Rα diminished IL-4 signaling and the Th2 response and enhanced the Th1 response under suboptimal polarizing conditions. In nontransgenic CD4 T cells, blocking IL-4Rα with Abs had the same effect in an Ab dose-dependent manner. Conversely, Hlx haploinsufficiency caused higher expression of IL-4Rα to favor Th2 cell differentiation. Thus, the IL-4Rα level on naive CD4 T cells is genetically controlled by Hlx and determines the ratio of Th1 and Th2 cell differentiation.

This article first appeared in the February 1, 2006 issue of The Journal of Immunology, the member magazine of the The American Association of Immunologists, and is reprinted with permission.

Copyright © 2006 by The American Association of Immunologists, Inc.

Citation Information
Mikhalkevich N, Becknell B, Caligiuri MA, Bates MD, Harvey R, Zheng WP. Responsiveness of naive CD4 T cells to polarizing cytokine determines the ratio of Th1 and Th2 cell differentiation. J Immunol 2006;176(3):1553-1560.