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Apoptotic cells induce dendritic cell-mediated suppression via interferon-γ-induced IDO.
- Source :
- Immunology; May2008, Vol. 124 Issue 1, p89-101, 13p, 9 Graphs
- Publication Year :
- 2008
-
Abstract
- Dendritic cells (DC) are sensitive to their local environment and are affected by proximal cell death. This study investigated the modulatory effect of cell death on DC function. Monocyte-derived DC exposed to apoptotic Jurkat or primary T cells failed to induce phenotypic maturation of the DC and were unable to support CD4<superscript>+</superscript> allogeneic T-cell proliferation compared with DC exposed to lipopolysaccharide (LPS) or necrotic cells. Apoptotic cells coincubated with LPS- or necrotic cell-induced mature DC significantly suppressed CD80, CD86 and CD83 and attenuated LPS-induced CD4<superscript>+</superscript> T-cell proliferation. Reduced levels of interleukin-12 (IL-12), IL-10, IL-6, tumour necrosis factor-α and interferon-γ (IFN-γ) were found to be concomitant with the suppressive activity of apoptotic cells upon DC. Furthermore, intracellular staining confirmed IFN-γ expression by DC in association with apoptotic environments. The specific generation of IFN-γ by DC within apoptotic environments is suggestive of an anti-inflammatory role by the induction of indoleamine 2,3-dioxygenase (IDO). Both neutralization of IFN-γ and IDO blockade demonstrated a role for IFN-γ and IDO in the suppression of CD4<superscript>+</superscript> T cells. Moreover, we demonstrate that IDO expression within the DC was found to be IFN-γ-dependent. Blocking transforming growth factor-β (TGF-β) also produced a partial release in T-cell proliferation. Our study strongly suggests that apoptosis-induced DC suppression is not an immunological null event and two prime mediators underpinning these functional effects are IFN-γ-induced IDO and TGF-β. [ABSTRACT FROM AUTHOR]
- Subjects :
- DENDRITIC cells
APOPTOSIS
INTERFERONS
NECROSIS
TOLERATION
CELLS
Subjects
Details
- Language :
- English
- ISSN :
- 00192805
- Volume :
- 124
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 31641845
- Full Text :
- https://doi.org/10.1111/j.1365-2567.2007.02743.x