Ido expression by dendritic cells: tolerance and tryptophan catabolism

Mellor, Andrew L.; Munn, David H.

doi:10.1038/nri1457

Cited by 2,079 publications

(2,052 citation statements)

References 149 publications

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“…24 The overexpression of IDO can suppress immune responses by blocking T-cell proliferation locally, 25 and its activity can be inhibited by the competitive inhibitor 1-MT. 26 In our experiments, 1-MT could marginally restore IFN-c production, suggesting that the suppressive effect of PF is mediated by IDO and additional soluble factors.…”

Section: Pf Inhibits the Functions Of T Cells And Differentiation Of mentioning

confidence: 46%

Pleural fluid from tuberculous pleurisy inhibits the functions of T cells and the differentiation of Th1 cells via immunosuppressive factors

Liu

et al. 2011

Cell Mol Immunol

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Immunosuppressive mediators in tuberculosis pleurisy (pleural fluid (PF)) are associated with the course of disease, but they remain poorly defined. To study the local immune status of patients with tuberculosis pleurisy, we examined the effect of PF on the functions of T cells and the differentiation of Th1 cells. PF could inhibit the ability of T cells to produce cytokines. However, tumor-necrosis factor (TNF)-a derived from non-T cells was not impaired. Further analysis indicated that cell activation and cell cycle progression were also suppressed. Moreover, PF could inhibit Th1 cell differentiation. Importantly, we found that inhibitors of indoleamine 2,3-dioxygenase (IDO) and adenosine and neutralizing antibodies against IL-10 and transforming growth factor (TGF)-b could reverse cytokine production, suggesting that IDO, adenosine, IL-10 and Transforming growth factor-b1 in PF might take part in impairing T-cell functions. Taken together, our data demonstrate for the first time that several immunopathological factors participate in the downregulation of T-cell functions in local PF.

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Section: Pf Inhibits the Functions Of T Cells And Differentiation Of mentioning

confidence: 46%

Pleural fluid from tuberculous pleurisy inhibits the functions of T cells and the differentiation of Th1 cells via immunosuppressive factors

Liu

et al. 2011

Cell Mol Immunol

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“…11 Immunostaining for IDO in the different organs demonstrated higher numbers of IDO þ cells in B cell-(GC staining) and T-cell areas of Mes LNs than in the other organs, as well as higher levels in Mes LNs of macaques progressing faster to AIDS (Figures 2b and d). Similar to TGF-b, we found greater numbers of IDO þ cells in the GALT of non-controllers than in controllers (Figure 3b).…”

Section: Resultsmentioning

confidence: 93%

“…It has been also shown that IDO is strongly expressed in macrophages and dendritic cells (DCs). 11 Herein, IDO immunostaining identified cells displaying a non-lymphoid morphological phenotype (Figure 2b). Thus, our data identified IDO and TGF-b in the lymphoid tissues as potential markers for AIDS progression, and these mediators might contribute to a significant extent to immunosuppression or blunting the local antiviral defenses.…”

Section: Resultsmentioning

confidence: 98%

“…Thus, TGF-b could be the arming signal 1 and the death molecules (signal 2), the executioners of the effector/memory CD8 þ T cells in Mes LNs. Moreover, given that IDO is responsible for downmodulating T-cell proliferation, 11 while PD-1 limits glucose metabolism, 37 their concerted expression may be a multi-pronged strategy to enforce T lymphocyte inhibition by disrupting cellular metabolism which is required for cell survival. Thus, triggering multiple negative regulators of T-cell activation will likely be far more effective at dysregulating T-cell activation during SIV infection than the actions of any single inhibitor.…”

Section: Discussionmentioning

confidence: 99%

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TGF-β in intestinal lymphoid organs contributes to the death of armed effector CD8 T cells and is associated with the absence of virus containment in rhesus macaques infected with the simian immunodeficiency virus

et al. 2007

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SIV-infected macaques exhibit distinct rates of progression to AIDS and despite significant increases in CD8 þ T cells, immune cells fail to control and eradicate SIV in vivo. Here, we investigated the interplay between viral reservoir sites, CD8 þ T-cell activation/death and outcome. Our data provide strong evidence that mesenteric (Mes) lymph nodes represent major reservoirs not only for SIV-infected macaques progressing more rapidly toward AIDS but also in controllers. We demonstrate that macaques progressing faster display greater expression of TGF-b and Indoleamine 2,3 dioxygenase in particular in intestinal tissues associated with a phosphorylation of the p53 protein on serine 15 in CD8 þ T cells from Mes lymph nodes. These factors may act as a negative regulator of CD8 þ T-cell function by inducing a Bax/Bak/Puma-dependent death pathway of effector/ memory CD8 þ T cells. Greater T-cell death and viral dissemination was associated with a low level of TIA-1 þ expressing cells. Finally, we provide evidence that abrogation of TGF-b in vitro enhances T-cell proliferation and reduces CD8 þ T-cell death. Our data identify a mechanism of T-cell exhaustion in intestinal lymphoid organs and define a potentially effective immunological strategy for the modulation of progression to AIDS. Cell Death and Differentiation (2007) 14, 1747-1758; doi:10.1038/sj.cdd.4402192; published online 6 July 2007Virus production in Human Immunodeficiency Virus 1 (HIV-1)-infected individuals is largely the result of a dynamic process involving continuous rounds of de novo infection and replication in CD4 þ cells with rapid turnover of both free virus and virus producing cells. Moreover, an increasing body of evidence suggests that reservoirs, cell types or anatomical sites ('sanctuaries'), represent a major barrier to virus eradication. 1 HIV-specific CD8 þ T lymphocytes (CTL) are considered crucial in the control of viral replication. 2 Excessive induction of apoptosis has been proposed as one major mechanism of abnormal T-cell response during HIV and Simian Immunodeficiency Virus (SIV) infections. 3 However, most studies, which investigated the potential relationship between HIV and SIV infections and apoptosis have focused on cells from peripheral blood, rather than on cells from lymphoid organs.Peripheral lymphoid tissues such as the axillary and inguinal (Ing) lymph nodes (LNs), which drain the arms and legs, respectively, and the spleen, are considered major sites of HIV/SIV replication. 4 Accumulating data also indicate that gut-associated lymphoid tissue (GALT), which contains inductive sites, Peyer's patches and mesenteric (Mes) LNs, and effectors sites located within lamina propria and epithelium of the intestinal wall, is also an early and predominant tissue site of viral replication and may be a reservoir for HIV/SIV. 5,6 Because T cells from the GALT are required to maintain a state of immunological tolerance toward a myriad of dietary and resident bacterial antigens, the chronic exposure of HIV/ SIV-specific antigens coul...

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“…High expression of IDO results in an immunosuppressive tumor microenvironment with impaired activity of effector T cells, increased differentiation of regulatory T (T reg ) cells and decreased dendritic cell (DC) functions. 26 Treatment with IDO inhibitor reversed suppression by decreasing numbers of myeloid-derived suppressor cells (MDSCs) and T reg s. 27 Expression of IDO is a critical resistance mechanism to CTLA-4 blockade and dual inhibition with CTLA-4 and PD-1 or PD-L1 blockade leads to synergistic antitumor effects in melanoma models. 28,29 Therefore, preclinical data provides a strong theoretical basis for exploration of clinical combinations of IDO inhibitors and immune checkpoint inhibitors.…”

Section: Combination Strategiesmentioning

confidence: 99%

Management of Italian Patients With Advanced Non–Small-Cell Lung Cancer After Second-Line Treatment: Results of the Longitudinal Phase of the LIFE Observational Study

Marinis

Ardizzoni

Fontanini

et al. 2014

Clinical Lung Cancer

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Ido expression by dendritic cells: tolerance and tryptophan catabolism

Cited by 2,079 publications

References 149 publications

Pleural fluid from tuberculous pleurisy inhibits the functions of T cells and the differentiation of Th1 cells via immunosuppressive factors

Pleural fluid from tuberculous pleurisy inhibits the functions of T cells and the differentiation of Th1 cells via immunosuppressive factors

TGF-β in intestinal lymphoid organs contributes to the death of armed effector CD8 T cells and is associated with the absence of virus containment in rhesus macaques infected with the simian immunodeficiency virus

Management of Italian Patients With Advanced Non–Small-Cell Lung Cancer After Second-Line Treatment: Results of the Longitudinal Phase of the LIFE Observational Study

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