Tryptophan Catabolism and Regulation of Adaptive Immunity

Mellor, Andrew L.; Munn, David H.

doi:10.4049/jimmunol.170.12.5809

Cited by 189 publications

(143 citation statements)

References 40 publications

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“…Recently, Mellor and Munn [40] proposed in a review article as mechanism of action of Treg that they might condition APC to acquire regulatory function by inducing the APC to express IDO. They based this hypothesis on the observations made on DC, which are able to suppress T cell responses upon IDO expression [41]. Our data do not confirm this speculation, since the transfer of Treg, which was able to rescue from abortion, did not change the IDO levels, at least at the mRNA level (Fig.…”

Section: Resultscontrasting

confidence: 55%

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

et al. 2005

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The mechanisms underlying immune tolerance during pregnancy are poorly understood. In this regard, Treg seem to play an important role in mediating maternal tolerance to the fetus. We proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus after observing diminished number and function of Treg in abortion-prone mice. We further confirmed the protective role of Treg during pregnancy by transferring pregnancy-induced Treg into abortion-prone mice, which prevented rejection. Here, we analyzed the mechanisms involved in Treg-mediated protection. As expected, Treg therapy prevented abortion, while expanding the peripheral and thymic Treg population. Surprisingly, the decidual levels of the Th1 cytokines IFN-c and TNF-a were not diminished after therapy. Interestingly, the mRNA levels of leukemia inhibitory factor, TGF-b and heme oxygenase-1 at the fetal-maternal interface were dramatically up-regulated after Treg transfer, while the levels of indolamine 2,3-dioxygenase remained unchanged. Our data suggest that Treg treatment can not prevent T cell infiltration or high Th1 levels but is able to create a privileged tolerant microenvironment at the fetal-maternal interface, further shedding light onto the molecular mechanisms involved in pregnancy tolerance.

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Section: Resultscontrasting

confidence: 55%

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

et al. 2005

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“…For inhibition of contact hypersensitivity responses by UV-induced suppressor T cells, IL-10 production seems to be involved (14). Recently, the tryptophan-degrading enzyme, indoleamine 2,3-dioyxgenase (IDO), has been identified to play a role in the regulation of T cell function (51). It was demonstrated that ligation of CD80/CD86 on human DCs by CD4 ϩ T cells induced IDO activity, which allowed DCs to suppress the proliferation of CD4 and CD8 T cells (52).…”

Section: Discussionmentioning

confidence: 99%

An Important Role of CD80/CD86-CTLA-4 Signaling during Photocarcinogenesis in Mice

Loser

Scherer

Krummen

et al. 2005

The Journal of Immunology

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Although previous studies have shown that altered B7 costimulation plays a critical role in UV irradiation-induced regulation of immunity, the individual roles of the B7 receptors (CD28 and CTLA-4) or the B7 family members (CD80 and CD86) have not been explored. Thus, we investigated CTLA-4 signaling during photocarcinogenesis of chronically UV-B-exposed mice using an antagonistic anti-CTLA-4 Ab. Anti-CTLA-4-treated mice developed significantly fewer UV-induced tumors. Moreover, anti-CTLA-4 treatment induced long-lasting protective immunity because progressively growing UV tumors inoculated into anti-CTLA-4- and UV-treated mice that had not developed tumors were rejected. Next, we used mice deficient for CD80, CD86, or both in photocarcinogenesis studies to assess the relative contributions of these CTLA-4 ligands. Double-deficient mice showed significantly reduced UV-induced skin tumor development, whereas CD86−/− mice produced skin cancer earlier compared with CD80−/− and control mice. The growth of UV-induced tumors appears to be controlled by UV-induced suppressor T cells, because CD80−/−/CD86−/− mice had strongly reduced numbers of UV-induced CD4+CD25+ suppressor T cells. In vitro, CTLA-4 blockade inhibited the suppressor activity of UV-induced CD4+CD25+ T cells, suggesting that reduced photocarcinogenesis might be due to decreased numbers or function of suppressor T cells. Together, these data indicate that blocking CD80/86-CTLA-4 signaling induced immune protection against the development of UV-induced skin tumors. Furthermore, CD86-mediated costimulation appears to play a more critical role in the protection against photocarcinogenesis than CD80.

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“…4C). In addition, we examined the influence of IL-10 on expression of IDO, which regulates T cell proliferation and survival (27,28). Cytofluorimetric and Western blot analyses revealed that LPS-exposed DCs upregulate IDO in the presence of cmvIL-10 or hIL-10 (Fig.…”

Section: Two Distinct Groups Of Cmvil-10-sensitive Molecules In Dcsmentioning

confidence: 99%

Shaping Phenotype, Function, and Survival of Dendritic Cells by Cytomegalovirus-Encoded IL-10

Raftery

Wieland

Gronewald

et al. 2004

The Journal of Immunology

120

122

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Human dendritic cells (DCs) are essential for the antiviral immune response and represent a strategically important target for immune evasion of viruses, including human CMV (HCMV). Recently, HCMV has been discovered to encode a unique IL-10 homologue (cmvIL-10). In this study we investigated the capacity of cmvIL-10 to shape phenotype, function, and survival of DCs. For comparison we included human IL-10 and another IL-10 homologue encoded by EBV, which does not directly target DCs. Interestingly, cmvIL-10 strongly activated STAT3 in immature DCs despite its low sequence identity with human IL-10. For most molecules cmvIL-10 blocked LPS-induced surface up-regulation, confirming its role as an inhibitor of maturation. However, a small number of molecules on LPS-treated DCs including IDO, a proposed tolerogenic molecule, showed a different behavior and were up-regulated in response to cmvIL-10. Intriguingly, the expression of C-type lectin DC-specific ICAM-grabbing nonintegrin, a receptor for HCMV infection found exclusively on DCs, was also enhanced by cmvIL-10. This phenotypic change was mirrored by the efficiency of HCMV infection. Moreover, DCs stimulated with LPS and simultaneously treated with cmvIL-10 retained the function of immature DCs. Finally, cmvIL-10 increased apoptosis associated with DC maturation by blocking up-regulation of the antiapoptotic long form cellular FLIP. Taken together, these findings show potential mechanisms by which cmvIL-10 could assist HCMV to infect DCs and to impair DC function and survival.

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Tryptophan Catabolism and Regulation of Adaptive Immunity

Cited by 189 publications

References 40 publications

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

An Important Role of CD80/CD86-CTLA-4 Signaling during Photocarcinogenesis in Mice

Shaping Phenotype, Function, and Survival of Dendritic Cells by Cytomegalovirus-Encoded IL-10

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