Back to Search
Start Over
Role of IFN-gamma in Th1 differentiation: IFN-gamma regulates IL-18R alpha expression by preventing the negative effects of IL-4 and by inducing/maintaining IL-12 receptor beta 2 expression
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 168(12)
- Publication Year :
- 2002
-
Abstract
- Two key events occur during the differentiation of IFN-gamma-secreting Th1 cells: up-regulation of IL-12Rbeta2 and IL-12-driven up-regulation of IL-18Ralpha. We previously demonstrated that IL-12-driven up-regulation of IL-18Ralpha expression is severely impaired in IFN-gamma(-/-) mice. However, it was unclear from these studies how IFN-gamma influenced IL-18Ralpha since IFN-gamma alone had no direct effect on IL-18Ralpha expression. In the absence of IL-4, IL-12-dependent up-regulation of IL-18Ralpha/IL-12Rbeta2 was independent of IFN-gamma. However, in the presence of IL-4, IFN-gamma functions to limit the negative effects of IL-4 on both IL-18Ralpha and IL-12Rbeta2. Neutralization of IL-4 restored IL-12-driven up-regulation of IL-18Ralpha/IL-12Rbeta2 in an IFN-gamma-independent fashion. In the absence of both IL-12 and IL-4, IFN-gamma up-regulates IL-12beta2 expression and primes IFN-gamma-producing Th1 cells. When T cells were primed in the presence of IL-4, no correlation was found between the levels of expression of the IL-18Ralpha or the IL-12Rbeta2 and the capacity of these cells to produce IFN-gamma, suggesting that IL-4 may also negatively affect IL-12-mediated signal transduction and thus Th1 differentiation. These data clarify the role of IFN-gamma in regulation of IL-18Ralpha/IL-12Rbeta2 during both IL-12-dependent and IL-12-independent Th1 differentiation.
- Subjects :
- Mice, Inbred A
Immunology
Mice, Transgenic
Biology
Neutralization
Interferon-gamma
Mice
Adjuvants, Immunologic
Immunology and Allergy
Animals
Receptor
Interleukin 4
Cells, Cultured
Mice, Inbred BALB C
Receptors, Interleukin-18
Interleukin-18
Receptors, Interleukin-12
Cell Differentiation
Receptors, Interleukin
Th1 Cells
Interleukin-12
Cell biology
DNA-Binding Proteins
Mice, Inbred C57BL
Interleukin 12
Female
Interleukin-4
Signal transduction
Interleukin-18 Receptor alpha Subunit
Subjects
Details
- ISSN :
- 00221767
- Volume :
- 168
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....4d35a9e76f927242162efd54dad74e08