IGIF does not drive Th1 development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NFkappaB.
In these studies, IFN gamma-inducing factor (IGIF), unlike IL-12, did not drive Th1 development in BALB/c or C57BL/6 mice, but like IL-1alpha, potentiated IL-12-driven Th1 development in BALB/c mice. IGIF and IL-12 synergized for IFN gamma production from Th1 cells. Unlike IL-1alpha, IGIF had no effect on Th2 cells. IGIF signaled through IRAK, IL-1 receptor-associated kinase, to induce nuclear translocation of p65/p50 NFkappaB in Th1 cells. IL-1alpha had no effect on proliferation, cytokine production, or NFkappaB activation in Th1 cells but activated NFkappaB and proliferation in Th2 cells. Thus, Th1 and Th2 cells may differ in responsiveness and receptor expression for IL-1 family molecules. IGIF and IL-1alpha may differentially amplify Th1 and Th2 effector responses, respectively.
Robinson
D
D
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Shibuya
K
K
Mui
A
A
Zonin
F
F
Murphy
E
E
Sana
T
T
Hartley
S B
SB
Menon
S
S
Kastelein
R
R
Bazan
F
F
O'Garra
A
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D017252:CD3 Complex / Q000502:physiology; D016207:Cytokines / Q000008:administration & dosage / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation; D007369:Interferon Inducers / Q000008:administration & dosage; D007371:Interferon-gamma / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology; D053592:Interleukin-1 Receptor-Associated Kinases; D018664:Interleukin-12 / Q000008:administration & dosage / Q000502:physiology*; D020382:Interleukin-18; D019891:Leukopoiesis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism*; D050797:STAT4 Transcription Factor; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology*; D018418:Th2 Cells / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism
D017252:CD3 Complex; D016207:Cytokines; D004268:DNA-Binding Proteins; D007369:Interferon Inducers; D007375:Interleukin-1; D020382:Interleukin-18; D016328:NF-kappa B; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D007371:Interferon-gamma; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases