Innate IFN-γ is essential for programmed death ligand-1-mediated T cell stimulation following Listeria monocytogenes infection
In: Journal of immunology (Baltimore, Md. : 1950), Jg. 189 (2012-06-20), Heft 2
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Zugriff:
Although best characterized for sustaining T cell exhaustion during persistent viral infection, programmed death ligand-1 (PDL-1) also stimulates the expansion of protective T cells after infection with intracellular bacterial pathogens. Therefore, establishing the molecular signals that control whether PDL-1 stimulates immune suppression or activation is important as immune modulation therapies based on manipulating PDL-1 are being developed. In this study, the requirement for PDL-1 blockade initiated before infection with the intracellular bacterium Listeria monocytogenes in reducing pathogen-specific T cell expansion is demonstrated. In turn, the role of proinflammatory cytokines triggered early after L. monocytogenes infection in controlling PDL-1–mediated T cell stimulation was investigated using mice with targeted defects in specific cytokines or cytokine receptors. These experiments illustrate an essential role for IL-12 or type I IFNs in PDL-1–mediated expansion of pathogen-specific CD8+ T cells. Unexpectedly, direct stimulation by neither IL-12 nor type I IFNs on pathogen-specific CD8+ cells was essential for PDL-1–mediated expansion. Instead, the absence of early innate IFN-γ production in mice with combined defects in both IL-12 and type I IFNR negated the impacts of PDL-1 blockade. In turn, IFN-γ ablation using neutralizing Abs or in mice with targeted defects in IFN-γR each eliminated the PDL-1–mediated stimulatory impacts on pathogen-specific T cell expansion. Thus, innate IFN-γ is essential for PDL-1–mediated T cell stimulation.
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Innate IFN-γ is essential for programmed death ligand-1-mediated T cell stimulation following Listeria monocytogenes infection
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Autor/in / Beteiligte Person: | Ertelt, James M. ; Sing Sing Way ; Rowe, Jared H. |
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Zeitschrift: | Journal of immunology (Baltimore, Md. : 1950), Jg. 189 (2012-06-20), Heft 2 |
Veröffentlichung: | 2012 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) |
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