Responsiveness of naive CD4 T cells to polarizing cytokine determines the ratio of Th1 and Th2 cell differentiation.
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.
Mikhalkevich
Natallia
N
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, USA.
Becknell
Brian
B
Caligiuri
Michael A
MA
Bates
Michael D
MD
Harvey
Richard
R
Zheng
Wei-ping
WP
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000276:immunology; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics; D015847:Interleukin-4 / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019948:Receptors, Interleukin-4 / Q000037:antagonists & inhibitors / Q000276:immunology; D016192:Resting Phase, Cell Cycle / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology* / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics
D000906:Antibodies; D016207:Cytokines; C489999:Hlx protein, mouse; D018398:Homeodomain Proteins; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D014157:Transcription Factors; D015847:Interleukin-4