Cutting edge: ectopic expression of the IL-12 receptor-beta 2 in developing and committed Th2 cells does not affect the production of IL-4 or induce the production of IFN-gamma.
The IL-12 receptor-beta 2 (IL-12R beta 2) chain is expressed on Th1 cells and lost upon differentiation to the Th2 phenotype. This has been suggested as the basis for commitment of Th1 cells, because early differentiated Th2 cells do not reverse their phenotype and do not produce IFN-gamma on restimulation in the presence of IL-12. In this study, we ectopically expressed the IL-12 receptor-beta 2 (IL-12R beta 2) bicistronically with enhanced green fluorescent protein by retroviral infection in developing and committed Th2 cells. Restimulation of Th2 cells expressing this ectopic IL-12R beta 2 in the presence of IL-12 led to levels of IL-4 production similar to those in control Th2 cells. The expression of IL-12R beta 2 in Th2 cells did not lead to significant levels of IFN-gamma production, although IL-12-mediated STAT signaling and proliferation were restored. Thus, although the IL-12R beta 2 and IL-12-dependent STAT4 activation are required for Th1 responses, activation of this pathway is not sufficient to restore a Th1 phenotype in developing or committed Th2 cells.
Heath
V L
VL
Department of Immunobiology, DNAX Research Institute, Palo Alto, CA 94304, USA. Heath@DNAX.org
Showe
L
L
Crain
C
C
Barrat
F J
FJ
Trinchieri
G
G
O'Garra
A
A
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D015536:Down-Regulation / Q000276:immunology; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000378:metabolism* / Q000502:physiology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000502:physiology
D004268:DNA-Binding Proteins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma