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* David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642;
Ohio State University Comprehensive Cancer Center, Columbus, OH 43210;
Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229;
Victor Chang Cardiac Research Institute, St. Vincent’s Hospital, Darlinghurst, Australia; and
¶ Faculties of Medicine and Life Sciences, University of New South Wales, Kensington, Australia
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-4R
. The down-regulation of IL-4R diminished IL-4 signaling and the Th2 response and enhanced the Th1 response under suboptimal polarizing conditions. In nontransgenic CD4 T cells, blocking IL-4R with Abs had the same effect in an Ab dose-dependent manner. Conversely, Hlx haploinsufficiency caused higher expression of IL-4R to favor Th2 cell differentiation. Thus, the IL-4R level on naive CD4 T cells is genetically controlled by Hlx and determines the ratio of Th1 and Th2 cell differentiation.
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