Responsiveness of Naive CD4 T Cells to Polarizing Cytokine Determines the Ratio of Th1 and Th2 Cell Differentiation

• Published in: Journal of Immunology Vol. 176; no. 3; pp. 1553 - 1560
• Main Authors: Mikhalkevich, Natallia, Becknell, Brian, Caligiuri, Michael A, Bates, Michael D, Harvey, Richard, Zheng, Wei-ping
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.02.2006
• Subjects: Animals; Antibodies - pharmacology; CD4 Lymphocyte Count; Cell Differentiation - immunology; Cells, Cultured; Cytokines - physiology; Dose-Response Relationship, Drug; Down-Regulation - immunology; Heterozygote; Homeodomain Proteins - genetics; Interleukin-4 - physiology; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Receptors, Interleukin-4 - antagonists & inhibitors; Receptors, Interleukin-4 - immunology; Resting Phase, Cell Cycle - immunology; Signal Transduction - immunology; STAT6 Transcription Factor - metabolism; Th1 Cells - cytology; Th1 Cells - metabolism; Th2 Cells - cytology; Th2 Cells - metabolism; Transcription Factors - genetics
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.176.3.1553

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-4Ralpha. The down-regulation of IL-4Ralpha diminished IL-4 signaling and the Th2 response and enhanced the Th1 response under suboptimal polarizing conditions. In nontransgenic CD4 T cells, blocking IL-4Ralpha with Abs had the same effect in an Ab dose-dependent manner. Conversely, Hlx haploinsufficiency caused higher expression of IL-4Ralpha to favor Th2 cell differentiation. Thus, the IL-4Ralpha level on naive CD4 T cells is genetically controlled by Hlx and determines the ratio of Th1 and Th2 cell differentiation.