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Apoptotic cells induce dendritic cell-mediated suppression via interferon-γ-induced IDO

Williams, Charlotte A.; Harry, Rachel A.; McLeod, Julie D.

Authors

Charlotte A. Williams

Rachel A. Harry

Julie D. McLeod



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+ 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+ 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+ 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. © 2007 The Authors.

Citation

Williams, C. A., Harry, R. A., & McLeod, J. D. (2008). Apoptotic cells induce dendritic cell-mediated suppression via interferon-γ-induced IDO. Immunology, 124(1), 89-101. https://doi.org/10.1111/j.1365-2567.2007.02743.x

Journal Article Type Article
Publication Date May 1, 2008
Journal Immunology
Print ISSN 0019-2805
Electronic ISSN 1365-2567
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 124
Issue 1
Pages 89-101
DOI https://doi.org/10.1111/j.1365-2567.2007.02743.x
Keywords apoptosis, dendritic cells, interferon, necrosis, tolerance
Public URL https://uwe-repository.worktribe.com/output/1022736
Publisher URL http://dx.doi.org/10.1111/j.1365-2567.2007.02743.x




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