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IL-12 and type-I IFN synergize for IFN-gamma production by CD4 T cells, whereas neither are required for IFN-gamma production by CD8 T cells after Listeria monocytogenes infection.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2007 Apr 01; Vol. 178 (7), pp. 4498-505. - Publication Year :
- 2007
-
Abstract
- Differentiation of Ag-specific T cells into IFN-gamma producers is essential for protective immunity to intracellular pathogens. In addition to stimulation through the TCR and costimulatory molecules, IFN-gamma production is thought to require other inflammatory cytokines. Two such inflammatory cytokines are IL-12 and type I IFN (IFN-I); both can play a role in priming naive T cells to produce IFN-gamma in vitro. However, their role in priming Ag-specific T cells for IFN-gamma production during experimental infection in vivo is less clear. In this study, we examine the requirements for IL-12 and IFN-I, either individually or in combination, for priming Ag-specific T cell IFN-gamma production after Listeria monocytogenes (Lm) infection. Surprisingly, neither individual nor combined defects in IL-12 or IFN-I signaling altered IFN-gamma production by Ag-specific CD8 T cells after Lm infection. In contrast, individual defects in either IL-12 or IFN-I signaling conferred partial ( approximately 50%) reductions, whereas combined deficiency in both IL-12 and IFN-I signaling conferred more dramatic (75-95%) reductions in IFN-gamma production by Ag-specific CD4 T cells. The additive effects of IL-12 and IFN-I signaling on IFN-gamma production by CD4 T cells were further demonstrated by adoptive transfer of transgenic IFN-IR(+/+) and IFN-IR(-/-) CD4 T cells into normal and IL-12-deficient mice, and infection with rLm. These results demonstrate an important dichotomy between the signals required for priming IFN-gamma production by CD4 and CD8 T cells in response to bacterial infection.
- Subjects :
- Adoptive Transfer
Animals
CD4-Positive T-Lymphocytes transplantation
Interferon Type I genetics
Interferon-gamma metabolism
Interleukin-12 genetics
Mice
Mice, Mutant Strains
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Interferon Type I physiology
Interleukin-12 physiology
Listeria monocytogenes
Listeriosis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 178
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 17372008
- Full Text :
- https://doi.org/10.4049/jimmunol.178.7.4498