Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

Beutelspacher, Sven C.; Pillai, Radhakrishna G.; Watson, Martin P.; Tan, Peng; Tsang, Julia Yuen Shan; McClure, Myra O.; George, Andrew J.T.; Larkin, Frank

doi:10.1002/eji.200535238

Cited by 154 publications

(144 citation statements)

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“…They have also found that tryptophan catabolism prevents T cell-driven complement activation and inflammation during pregnancy (11), suggesting that IDO plays a key role in placenta immune privilege. IDOexpressing dendritic cells suppress allogeneic T cell proliferation in vitro by tryptophan metabolites (7) and IDO action attenuates allograft injury or rejection (12)(13)(14). Tryptophan catabolism also induces regulatory cells and is a means by which CTLA-4 signaling functions in vivo (15)(16)(17) while inhibiting IDO restores antitumor immunity (18).…”

Section: Suppression Of Memory Cd8 T Cell Generation Andmentioning

confidence: 99%

Suppression of Memory CD8 T Cell Generation and Function by Tryptophan Catabolism

Liu

Dai

et al. 2007

The Journal of Immunology

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Dendritic cell-derived indoleamine 2,3-dioxygenase (IDO) suppresses naive T cell proliferation and induces their apoptosis by catalyzing tryptophan, and hence is essential for the maintenance of peripheral tolerance. However, it is not known whether memory T cells are subject to the regulation by IDO-mediated tryptophan catabolism, as memory T cells respond more rapidly and vigorously than their naive counterparts and are resistant to conventional costimulatory blockade. In this study, we present the evidence that memory CD8+ T cells are susceptible to tryptophan catabolism mediated by IDO. We found that overexpression of IDO in vivo attenuated the generation of both central memory CD8+ T cells (TCM) and effector memory CD8+ T cells (TEM) while suppressing IDO activity promoted their generation. Moreover, IDO overexpression suppressed the effector function of TCM cells or TCM cell-mediated allograft rejection as well as their proliferation in vivo. Interestingly, TCM cells were resistant to apoptosis induced by tryptophan catabolism. However, IDO overexpression did not suppress the effector function of TEM cells or TEM cell-mediated allograft rejection, suggesting that TEM cells, unlike TCM cells, do not require tryptophan for their effector function once they are generated. This study provides insight into the mechanisms underlying the differential regulation of memory T cell responsiveness and has clinical implications for vaccination or tolerance induction.

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Section: Suppression Of Memory Cd8 T Cell Generation Andmentioning

confidence: 99%

Suppression of Memory CD8 T Cell Generation and Function by Tryptophan Catabolism

Liu

Dai

et al. 2007

The Journal of Immunology

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“…3,4 Expressed transgenic proteins capable of prolonging corneal allograft survival in animal models include mammalian interleukin 10, 5 the p40 subunit of interleukin 12, 6 interleukin 4 (albeit not in all studies), [7][8][9] soluble tumour necrosis factor receptor, 10 endostatin-kringle 5 fusion protein (E-Kr5), 11 soluble CTLA4 or CTLA4-Ig constructs 12,13 and indoleamine 2,3-dioxygenase. 14 Many studies in which modulation of corneal graft rejection by gene transfer was the experimental objective have utilized non-viral or replication-deficient adenovirus vectors to transduce the cornea, so that long-term expression of the transgene was not achieved and the grafts ultimately failed. Integrative vectors such as recombinant adeno-associated virus (AAV) and lentivirus hold greater promise for achieving long-term transgene expression and corneal graft survival than do non-viral or non-integrative viral vectors.…”

Section: Introductionmentioning

confidence: 99%

Lentivirus-mediated gene transfer to the rat, ovine and human cornea

et al. 2007

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Gene therapy of the cornea shows promise for modulating corneal transplant rejection but the most appropriate vector for gene transfer has yet to be determined. We investigated a lentiviral vector (LV) for its ability to transduce corneal endothelium. A lentivector expressing enhanced yellow fluorescent protein (eYFP) under the control of the Simian virus type 40 early promoter (LV-SV40-eYFP) transduced 80-90% of rat, ovine and human corneal endothelial cells as detected by fluorescence microscopy. The kinetics of gene expression varied among species, with ovine corneal endothelium showing a relative delay in detectable reporter gene expression compared with the rat or human corneal endothelium. Vectors containing the myeloproliferative sarcoma virus promoter or the phosphoglycerate kinase promoter were not significantly more effective than LV-SV40-eYFP. The stability of eYFP expression in rat and ovine corneas following ex vivo transduction of the donor cornea was assessed following orthotopic corneal transplantation. Following transduction ex vivo, eYFP expression was maintained in corneal endothelial cells for at least 28 days after corneal transplantation in the sheep and 460 days in the rat. Thus, rat, ovine and human corneal endothelial cells were efficiently transduced by the LV, and gene expression appeared stable over weeks in vivo. Gene Therapy (2007) 14, 760-767.

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Section: Corneal Transplantationmentioning

confidence: 99%

“…The reduction of tryptophan is thought to halt activated T cells in the cell cycle, which encourages immune tolerance of the transplanted cornea. This same research group also evaluated the effect of IDO transduction on donor corneas ex vivo prior to transplantation and found significant prolongation of corneal allograft survival compared to controls [40].Another group found that the transfer of an anti-apoptotic gene, bcl-xL, using a lentivirus vector was effective at inhibiting apoptosis in the corneal endothelium in vitro in a rodent model, as well as significantly enhancing corneal graft survival in vivo [41]. Another application of gene therapy use for corneal transplantation involves the preservation of corneal endothelial cell density in corneal tissue that is stored at eye banks.…”

mentioning

confidence: 99%

Corneal Gene Therapy in Veterinary Medicine: A Review

Bosiack¹

2013

J Veterinar Sci Technol

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The cornea is an ideal target for gene therapy due to its accessibility, immune-privileged nature, and ability to perform frequent non-invasive assessment. Gene therapy has been studied in animal models of ocular corneal graft rejection, neovascularization, wound healing, fibrosis, macular degeneration, optic neuropathy, and retinal degeneration. Medical research has widely used animal models in the pursuit of improved therapeutic strategies intended to aid people. In this review we summarize the vectors currently used in ocular gene therapy and the potential applications of emerging new strategies for use in veterinary medicine. diseases. The cornea represents one of the most evolutionary conserved anatomic components across mammals with many shared pathological processes in various species. Corneal gene therapy is therefore an ideal target for collaborative biomedical research. Corneal Gene Therapy in Veterinary MedicineThe potential therapeutic applications of gene therapy are vast. A major advantage of gene therapy over the use of conventional drugs is the prospect of curing disease rather than providing transient relief by suppression of disease symptoms. Replacing defective genes with functional genes through the use of gene therapy offers the prospect for long-term therapeutic benefits without repeated drug application. Successful vision restoration through the use of gene therapy in patients affected with LCA has demonstrated the ability of gene therapy to potentially cure ocular disease and prevent long-term blindness [3,4]. Further research in gene therapy is needed to develop treatments for other vision-impairing ocular diseases.The cornea is an ideal target for gene therapy due to its accessibility, immune-privileged nature, and ability to perform frequent noninvasive assessment [5,6]. Gene therapy has been studied in animal models of ocular corneal graft rejection, neovascularization, wound healing, fibrosis, macular degeneration, optic neuropathy, and retinal degeneration [6][7][8][9][10][11][12][13][14]. The success of corneal gene therapy depends on the type of vector, the extent of therapeutic gene expression, and adverse immune responses [15]. Vectors Conventional vectorsSeveral viral as well as non-viral vectors have been developed to transport genetic material into cells, each of which has advantages and limitations (Table 1) Several studies have assessed the efficacy of Adenovirus (AV) vectors for corneal gene therapy [6]. AV vectors have been shown to effectively deliver genes to the rodent cornea; however, they provide short-term transgene expression and stimulate moderate to severe inflammation [16,17]. Retroviral vectors can successfully deliver genes into the cornea but are not capable of transducing non-dividing cells [18]. Like adenovirus, retroviral vectors have also been shown to stimulate mild-to-severe inflammatory responses and have oncogenic potential due to their integration near proto-oncogenes, making them undesirable [6,19]. Lentiviral vectors appear to be safer tha...

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Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

Cited by 154 publications

References 56 publications

Suppression of Memory CD8 T Cell Generation and Function by Tryptophan Catabolism

Suppression of Memory CD8 T Cell Generation and Function by Tryptophan Catabolism

Lentivirus-mediated gene transfer to the rat, ovine and human cornea

Corneal Gene Therapy in Veterinary Medicine: A Review

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