IL-4 and IL-13 production in differentiated T helper type 2 cells is not IL-4 dependent.
CD4+ T cell differentiation into cells capable of producing IL-4 and IL-13 (Th2 cells) requires the presence of IL-4 and is STAT-6 dependent. Here we show that IL-4 is not required for IL-4 or IL-13 production by Th2 cells. Anti-IL-4 or anti-IL-4R Ab did not diminish IL-4 production by Th2 cells in response to TCR-mediated stimulation, nor did IL-4 enhance IL-4 production in response to stimulation of Th2 cells with limiting amounts of Ag. Th2 cells prepared from IL-4 knockout mice were capable of producing IL-13 mRNA in response to stimulation with immobilized anti-CD3. IL-4 did not increase IL-13 mRNA expression. Despite the failure of IL-4 to effect IL-4 production by primed Th2 cells, a STAT-6 binding element was demonstrated in the IL-4 promoter. The authenticity of this element was demonstrated by oligonucleotide competition, by supershifting with anti-STAT-6 Ab, and by IL-4-inducible effects on transcription of a reporter gene under the control of a multimerized element fused to an IL-4 minimal promoter. Nonetheless, an IL-4 promoter construct lacking the STAT-6 binding element was as effective as a construct containing this element in anti-CD3-induced reporter transcription. Thus, this element, if biologically active, must function at a step in T cell responsiveness distinct from the acute production of IL-4 by Th2 cells in response to Ag or anti-CD3.
Huang
H
H
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-1892, USA.
Hu-Li
J
J
Chen
H
H
Ben-Sasson
S Z
SZ
Paul
W E
WE
D000818:Animals; D019898:Autocrine Communication / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005246:Feedback; D018793:Interleukin-13 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology
D018793:Interleukin-13; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4