Roles of IL-4 and IFN-gamma in stabilizing the T helper cell type 1 and 2 phenotype.
It has previously been reported that Th1 CD4 T cell populations can be converted to IL-4 producers, whereas Th2 populations are refractory to IL-12-mediated IFN-gamma production. We have recently shown that CD30 is a marker for the IL-4 response and have therefore used CD30 here to study Th1 and Th2 commitment. We show that Th2 cell populations normally show a stable phenotype and fail to respond to IL-12 because of endogenous IL-4 production. IFN-gamma abrogates this antagonistic effect of IL-4 and permits the conversion of Th2 populations to IFN-gamma producers by IL-12. In the complete absence of IL-4, however, IFN-gamma is not required for this transformation, and Th1 cells generated by IL-12 become committed to the Th1 pathway and lose the ability to respond to IL-4. Thus, the balance between local IL-4 and IFN-gamma in an immune response is a key factor in determining the outcome of the CD4 effector T cell response.
Nakamura
T
T
Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT 06520, USA.
Lee
R K
RK
Nam
S Y
SY
Podack
E R
ER
Bottomly
K
K
Flavell
R A
RA
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002999:Clone Cells; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma