The Experts below are selected from a list of 579 Experts worldwide ranked by ideXlab platform
Jerry Y. Niederkorn - One of the best experts on this subject based on the ideXlab platform.
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Corneal Nerve Ablation Abolishes Ocular Immune Privilege by Downregulating CD103 on T Regulatory Cells.
Investigative ophthalmology & visual science, 2020Co-Authors: Sudha Neelam, Jerry Y. NiederkornAbstract:Purpose Severing corneal nerves during orthotopic corneal transplantation elicits the elaboration of the neuropeptide substance P (SP), which induces the generation of CD11c+ contrasuppressor (CS) cells. CS cells disable T regulatory cells (Tregs) that are induced when antigens enter the anterior chamber (AC), either by direct injection or by orthotopic corneal transplantation. This study examined the crucial cell surface molecules on Tregs that are adversely affected by CS cells that are generated by severing corneal nerves. Methods CS cells were induced by producing shallow 2.0-mm circular incisions in the corneal epithelium in BALB/c mice. CD8+ Tregs were generated by injecting ovalbumin into the AC. The effects of CS cells and SP on the expression and function of two cell surface molecules (CD103 and the receptor of interferon-γ) that are crucial for the induction and function of CD8+ Tregs were analyzed. Results SP converted CD11c+, but not CD11c- , dendritic cells (DCs) to CS cells. Severing corneal nerves resulted in a 66% reduction in the expression of CD103 on CD8+ AC-associated Immune deviation (ACAID) Tregs, and a 50% reduction in the interferon-γ receptor (IFN-γR). These effects could be mimicked in vitro by coculturing CS cells with CD8+ ACAID Tregs. Conclusions The elaboration of SP in response to corneal nerve ablation converts CD11c+ DCs to CS cells. CS cells disable CD8+ ACAID Tregs by downregulating two crucial cell surface molecules, CD103 and IFN-γR, by an SP-dependent pathway. Blocking this pathway may provide a means of restoring Ocular Immune Privilege in corneas subjected to corneal nerve injury.
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an IFN--dependent
2015Co-Authors: Dru S. Dace, Peter W. Chen, Hassan Alizadeh, Jerry Y. NiederkornAbstract: -
Ocular Immune Privilege and Ocular melanoma parallel universes or immunological plagiarism
Frontiers in Immunology, 2012Co-Authors: Jerry Y. NiederkornAbstract:Evidence of Immune Privilege in the eye was recorded almost 140 years ago, yet interest in Immune Privilege languished for almost a century. However, the past 35 years have witnessed a plethora of research and a rekindled interest in the mechanisms responsible for Immune Privilege in the anterior chamber of the eye. This research has demonstrated that multiple anatomical, structural, physiological, and immunoregulatory processes contribute to Immune Privilege and remind us of the enormous complexity of this phenomenon. It is widely accepted that Immune Privilege is an adaptation for reducing the risk of Immune-mediated inflammation in organs such as the eye and brain whose tissues have a limited capacity to regenerate. Recent findings suggest that Immune Privilege also occurs in sites where stem cells reside and raise the possibility that Immune Privilege is also designed to prevent the unwitting elimination of stem cells by Immune-mediated inflammation at these sites. Uveal melanoma arises within the eye and as such, benefits from Ocular Immune Privilege. A significant body of research reveals an intriguing parallel between the mechanisms that contribute to Immune Privilege in the eye and those strategies used by uveal melanoma cells to evade Immune elimination once they have disseminated from the eye and establish metastatic foci in the liver. Uveal melanoma metastases seem to have “plagiarized” the blueprints used for Ocular Immune Privilege to create “ad hoc Immune Privileged sites” in the liver.
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Health, USA Reviewed by:
2012Co-Authors: Rachel R Caspi, Joan Stein-streilein, Schepens Eye, Jerry Y. NiederkornAbstract: -
Cornea: Window to Ocular Immunology
Current immunology reviews, 2011Co-Authors: Jerry Y. NiederkornAbstract:The Ocular surface is continuously exposed to environmental agents such as allergens, pollutants, and microorganisms, which could provoke inflammation. However, an array of anatomical, physiological, and immunological features of the Ocular surface conspire to limit corneal inflammation and endow the eye with Immune Privilege. A remarkable example of Ocular Immune Privilege is the success of corneal allografts, which unlike all other forms of organ transplantation, survive without the use of systemic immunosuppressive drugs or MHC matching. This review describes the anatomical, physiological, and dynamic immunoregulatory processes that contribute to Immune Privilege.
Wayne J Streilein - One of the best experts on this subject based on the ideXlab platform.
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By Altering Ocular Immune Privilege, Bone Marrow–derived Cells Pathogenically Contribute to DBA/2J Pigmentary Glaucoma
2013Co-Authors: Michael G Anderson, Wayne J Streilein, Richard S Smith, Olga V Savinova, David V Serreze, Meredith Gregory, Simon W M JohnAbstract:Pigment dispersion syndrome causes iris pigment release and often progresses to elevated intraOcular pressure and pigmentary glaucoma (PG). Because melanin pigment can have adjuvant like properties and because the Gpnmb gene, which contributes to pigment dispersion in DBA/2J (D2) mice, is expressed in dendritic cells, we tested the hypothesis that Ocular Immune abnormalities participate in PG phenotypes. Strikingly, we show that D2 eyes exhibit defects of the normally immunosuppressive Ocular microenvironment including inability of aqueous humor to inhibit T cell activation, failure to support anterior chamber (AC)-associated Immune deviation, and loss of Ocular Immune Privilege. Histologic analysis demonstrates infiltration of inflammatory leukocytes into the AC and their accumulation within the iris, whereas clinical indications of inflammation are typically very mild to undetectable. Importantly, some of these abnormalities precede clinical indications of pigment dispersal, suggesting an early role in disease etiology. Using bone marrow chimeras, we show that lymphohematopoietic cell lineages largely dictate the progression of pigment dispersion, the ability of the eye to support induction of AC-associated Immune deviation, and the integrity of the blood/Ocular barrier. These results suggest previously unsuspected roles for bone marrow–derived cells and Ocular Immune Privilege in the pathogenesis of PG. Key words: inflammation • Immune tolerance • delayed hypersensitivity • anterior chamber • leukocyte
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Iris Pigment Epithelium Expressing CD86 (B7-2) Directly Suppresses T Cell Activation In Vitro via Binding to
2013Co-Authors: Cytotoxic Lymphocyte–associated T Antigen, Sunao Sugita, Wayne J StreileinAbstract:A monolayer of pigment epithelium (PE) lines the iris PE (IPE), ciliary body PE, and retina PE of the inner eye, an Immune-Privileged site. These neural crest-derived epithelial cells participate in Ocular Immune Privilege through poorly defined molecular mechanisms. Murine PE cells cultured from different Ocular tissues suppress T cell activation by differing mechanisms. In particular, IPE cells suppress primarily via direct cell to cell contact. By examining surface expression of numerous candidate molecules (tumor necrosis factor receptor [TNFR]1, TNFR2, CD36, CD40, CD47, CD80, CD86, PD-L1, CD95 ligand, and type I interferon receptor), we report that IPE cells uniquely express on their surface the costimulatory molecule CD86. When IPE were blocked with anti-CD86 or were derived from CD80/CD86 (but not CD80) knockout (KO) mice, the cells displayed reduced capacity to suppress T cell activation. IPE also failed to suppress activation of T cells in the presence of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) immunoglobulin or if the T cells were obtained from CTLA-4 (but not CD28) KO mice. We conclude that iris pigment epithelial cells constitutively express cell surface CD86, which enables the cells to contact inhibit T cells via direct interaction with CTLA-4. Thus, Ocular Immune Privilege is achieved in part by subversion of molecules that are usually used for conventional Immune costimulation. Key words: Immune Privilege • costimulatory molecules • T lymphocytes • inhibition • ey
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neural control of Ocular Immune Privilege
Annals of the New York Academy of Sciences, 2006Co-Authors: Wayne J Streilein, Shigeki Okamoto, Y Sano, A W TaylorAbstract:: Ocular Immune Privilege arises from interactions between the Immune apparatus and the eye itself, thereby providing Immune protection for the eye that is devoid of sight-threatening inflammation. On the one hand, antigens injected intraOcularly elicit deviant systemic Immune responses that are devoid of immunogenic inflammation (Anterior Chamber-Associated Immune Deviation, ACAID). On the other hand, the Ocular microenvironment (aqueous humor, secreted by cells that surround this chamber) suppresses intraOcular expression of immunogenic inflammation. Several lines of evidence indicate that Ocular Immune Privilege is under neural control. First, aqueous humor contains neuropeptides (α-MSH, VIP, CGRP) that inhibit and alter the functional properties of T lymphocytes and macrophages. Second, when corneal nerves are severed, the tissues surrounding the anterior chamber cease secreting immunosuppressive factors and ACAID fails-until the nerves regrow. Third, light deprivation abolishes the capacity of the anterior chamber to support ACAID induction, a process that is sensitive to neuropeptides and melatonin. The photoreceptor(s) responsible for ACAID are connected to the nervous system and may reside in the anterior segment and/or the retina. Thus, neural elements from the central nervous system and within the eye help to shape both the induction and the expression of Ocular immunity, thereby promoting Immune Privilege.
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qa 1 a nonclassical mhc molecule with immunomodulatory functions is ubiquitously expressed in the Immune Privileged anterior chamber of the eye
Ocular Immunology and Inflammation, 2005Co-Authors: Sharmila Masli, Wayne J StreileinAbstract:Purpose: To determine whether the MHC class Ib gene, Qa-1, is expressed in the tissues that surround the Immune-Privileged anterior chamber (AC) of the murine eye. Methods: Transcription of Qa-1 mRNA in BALB/c Ocular tissues was analyzed by reverse transcription-polymerase chain reaction. Expression of Qa-1 protein was assessed on Ocular frozen tissue sections by immunohistochemistry, and within aqueous humor by western blotting. Results: Transcription of Qa-1 was found in all tissues surrounding the AC of the eye. Immunohistological staining revealed Qa-1 expression on corneal endothelium, corneal epithelium, and lens epithelium. No soluble Qa-1 was detected in aqueous humor. Conclusions: Qa-1, unlike other MHC class I molecules, is ubiquitously expressed in tissues surrounding the AC of the eye, raising the possibility that Qa-1 plays a role in creating and maintaining Ocular Immune Privilege.
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Ocular Immune Privilege therapeutic opportunities from an experiment of nature
Nature Reviews Immunology, 2003Co-Authors: Wayne J StreileinAbstract:Most higher animals require sight for survival, yet even minor distortions of the visual axis can cause blindness. For this reason, intraOcular inflammation is incompatible with good vision. Nature has found a way to provide the eye with Immune protection against pathogens in a manner that greatly reduces the threat of inflammation-induced vision loss. Nature's way — known as 'Immune Privilege' — arises from anatomical, cellular and molecular specializations of the eye and the Immune system. Knowledge of these unique characteristics indicates new ways to prevent and treat autoImmune and immunopathogenic diseases of the eye, as well as other organs and tissues, and to promote acceptance of cornea and other types of solid-tissue allograft.
A W Taylor - One of the best experts on this subject based on the ideXlab platform.
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Negative regulators that mediate Ocular Immune Privilege
Journal of Leukocyte Biology, 2018Co-Authors: A W Taylor, Tat Fong NgAbstract:The Ocular microenvironment has adapted several negative regulators of inflammation to maintain Immune Privilege and health of the visual axis. Several constitutively produced negative regulators within the eye TGF-β2, α-melanocyte stimulating hormone (α-MSH), Fas ligand (FasL), and PD-L1 standout because of their capacity to influence multiple pathways of inflammation, and that they are part of promoting Immune tolerance. These regulators demonstrate the capacity of Immune Privilege to prevent the activation of inflammation, and to suppress activation of effector Immune cells even under conditions of Ocular inflammation induced by endotoxin and autoImmune disease. In addition, these negative regulators promote and expand Immune cells that mediate regulatory and tolerogenic immunity. This in turn makes the Immune cells themselves negative regulators of inflammation. This provides for a greater understanding of Immune Privilege in that it includes both molecular and cellular negative regulators of inflammation. This would mean that potentially new approaches to the treatment of autoImmune disease can be developed through the use of molecules and cells as negative regulators of inflammation.
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Ocular Immune Privilege and transplantation
Frontiers in Immunology, 2016Co-Authors: A W TaylorAbstract:Allografts are afforded a level of protection from rejection within Immune Privileged tissues. Immune Privileged tissues involve mechanisms that suppress inflammation, and promote Immune tolerance. There are anatomical features, soluble factors, membrane associated proteins, and alternative antigen presenting cells that contribute to allograft survival in the Immune Privileged tissue. This review presents the current understanding of how the mechanism of Ocular Immune Privilege promote tolerogenic activity by antigen presenting cells, and T cells in response to the placement of foreign antigen within the Ocular microenvironment. Discussed will be the unique anatomical, cellular and molecular mechanisms that lessen the chance for a graft destroying Immune responses within the eye. As more is understood about the molecular mechanisms of Ocular Immune Privilege greater is the potential in using these molecular mechanisms in therapies to prevent allograft rejection.
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Ocular Immune Privilege in the Year 2010: Ocular Immune Privilege and Uveitis
Ocular Immunology and Inflammation, 2010Co-Authors: A W Taylor, Henry J KaplanAbstract:The phrase “Immune Privilege” was coined by Peter Medawar to describe the absence of an Immune response to allografts placed into the anterior chamber of the eye or brain. We now understand that Immune Privilege is more than a passive microenvironment with a distinctive anatomical structure that holds back immunity. The Ocular microenvironment actively engages the Immune system with immunosuppressive biochemical mechanisms. The unique characteristics of Ocular Immune Privilege appear designed to protect the eye from damage while preserving foveal vision, thus providing the host with a definite survival advantage. However, the protection is not always sufficient and the eye becomes susceptible to uveitis. Uveitis is an intraOcular inflammatory disorder that encompasses a wide range of underlying etiologies. It may be idiopathic or associated with systemic disease or infection. Understanding the biochemistry of Immune Privilege has the potential to identify its weaknesses that allow for immunity to break th...
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Ocular Immune Privilege
Eye, 2009Co-Authors: A W TaylorAbstract:It has been over 60 years since the phrase Immune Privilege was used by Sir Peter Medawar to describe the lack of an Immune response against allografts placed into the Ocular microenvironment. Since then, we have come to understand that the mechanisms of Ocular Immune Privilege include unique anatomical features of a blood barrier and a lack of direct lymphatic drainage. Also, we know that the Ocular microenvironment is rich with immunosuppressive molecules that influence the activity of Immune cells. Moreover, the placement of foreign antigen into the Ocular microenvironment can induce a systemic form of tolerance to the foreign antigen called anterior chamber-associated Immune deviation (ACAID). Many soluble immunomodulators are found in aqueous humour, and are a mixture of growth factors, cytokines, neuropeptides, and soluble receptors. This is a continuously growing list. The mechanisms of Ocular Immune Privilege induce apoptosis, promote the production of anti-inflammatory cytokines, and mediate the activation of antigen-specific regulatory immunity. These mechanisms of Immune Privilege also attempt to impose themselves upon immunity within the uveitic eye. The adaptation of several anatomical and biochemical mechanisms to establish an Immune Privileged microenvironment within the eye makes the eye immunologically unique. It is a tissue site where we may learn how immunity is regulated in inflammation and at rest. Success in translating the lessons of Ocular Immune Privilege to other tissues has the potential to drastically change the therapy and clinical outcomes of autoImmune diseases and allograft survival.
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neural control of Ocular Immune Privilege
Annals of the New York Academy of Sciences, 2006Co-Authors: Wayne J Streilein, Shigeki Okamoto, Y Sano, A W TaylorAbstract:: Ocular Immune Privilege arises from interactions between the Immune apparatus and the eye itself, thereby providing Immune protection for the eye that is devoid of sight-threatening inflammation. On the one hand, antigens injected intraOcularly elicit deviant systemic Immune responses that are devoid of immunogenic inflammation (Anterior Chamber-Associated Immune Deviation, ACAID). On the other hand, the Ocular microenvironment (aqueous humor, secreted by cells that surround this chamber) suppresses intraOcular expression of immunogenic inflammation. Several lines of evidence indicate that Ocular Immune Privilege is under neural control. First, aqueous humor contains neuropeptides (α-MSH, VIP, CGRP) that inhibit and alter the functional properties of T lymphocytes and macrophages. Second, when corneal nerves are severed, the tissues surrounding the anterior chamber cease secreting immunosuppressive factors and ACAID fails-until the nerves regrow. Third, light deprivation abolishes the capacity of the anterior chamber to support ACAID induction, a process that is sensitive to neuropeptides and melatonin. The photoreceptor(s) responsible for ACAID are connected to the nervous system and may reside in the anterior segment and/or the retina. Thus, neural elements from the central nervous system and within the eye help to shape both the induction and the expression of Ocular immunity, thereby promoting Immune Privilege.
Andrew W. Taylor - One of the best experts on this subject based on the ideXlab platform.
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Melanocortin 5 Receptor Expression and Recovery of Ocular Immune Privilege after Uveitis.
Ocular immunology and inflammation, 2021Co-Authors: Ambika Manhapra, David Cluckey, Yoona Choe, Srujan Vajram, Andrew W. TaylorAbstract:Purpose: The therapeutic use of the RPE-neuropeptide α-MSH suppresses experimental autoImmune uveitis (EAU). This suppression is partially through the α-MSH melanocortin 5 receptor (MC5r). Therefor...
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The Neuropeptides of Ocular Immune Privilege, α-MSH and NPY, Suppress Phagosome Maturation in Macrophages.
ImmunoHorizons, 2018Co-Authors: Isaac J. Benque, Pu Xia, Robert Shannon, Andrew W. TaylorAbstract:The Ocular microenvironment has evolutionarily adapted several mechanisms of immunosuppression to minimize the induction of inflammation. Neuropeptides produced by the retinal pigment epithelial cells regulate macrophage activity. Two neuropeptides, α-melanocyte-stimulating hormone (α -MSH) and neuropeptide Y (NPY), are constitutively expressed by the retinal pigment epithelial cells. Together these two neuropeptides induce anti-inflammatory cytokine production in endotoxin-stimulated macrophages and suppress phagocytosis of unopsonized bioparticles. These neuropeptides do not suppress the phagocytosis of opsonized bioparticles; however, they do suppress phagolysosome activation or formation. In this report, we studied the possibility that α-MSH with NPY suppress phagosome maturation within macrophages using opsonized OVA-coated magnetic beads to isolate and analyze the phagosomes. The magnetic bead-containing intercellular vesicles were isolated and assayed for Rab5, Rab7, LAMP1, Iad, and OVA. The macrophages cotreated with α-MSH and NPY were suppressed in Rab7 recruitment to the phagosome with suppression in LAMP1 expression but not in Iad expression. The results demonstrated that the α-MSH/NPY cotreatment suppressed phagosome maturation. In addition, the a-MSH/NPY-cotreated macrophages were suppressed in their ability to Ag stimulate CD4+ T cell proliferation. These results imply a potential mechanism of Ocular Immune Privilege to divert Ag processing to prevent autoreactive effector T cells from binding their target cognate Ag within the Ocular microenvironment.
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localized retinal neuropeptide regulation of macrophage and microglial cell functionality
Journal of Neuroimmunology, 2011Co-Authors: Naoki Kawanaka, Andrew W. TaylorAbstract:The functionality of Immune cells is manipulated within the Ocular microenvironment to protect the sensitive and non-regenerating light-gathering tissue from the collateral damage of inflammation. This is mediated partly by the constitutive presence of immunomodulating neuropeptides. Treating primary resting macrophages with soluble factors produced by the posterior eye induced co-expression of Arginase1 and NOS2. The neuropeptides alpha-melanocyte stimulating hormone and Neuropeptide Y alternatively activated the macrophages to co-express Arginase1 and NOS2 like myeloid suppressor cells. Similar co-expressing cells were found within healthy, but not in wounded retinas. Therefore, the healthy retina regulates macrophage functionality to the benefit of Ocular Immune Privilege.
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Melanocortin 5 receptor and Ocular immunity.
Cellular and molecular biology (Noisy-le-Grand France), 2006Co-Authors: Andrew W. Taylor, Nobuyoshi Kitaichi, D. J. BirosAbstract:The nervous system contributes to the mechanisms of Ocular Immune Privilege by the constitutive presence of the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) in the eye. Alpha-MSH through the melanocortin 5 receptor (MC5r) mediates induction of CD4+ regulatory T cells that suppress in an antigen specific manner autoImmune disease. We investigated whether there was a role for MC5r expression in Ocular immunity and the natural induction of regulatory T cells that emerged following resolution of experimental autoImmune uveoretinitis (EAU). Unlike wild type mice, EAU in MC5r-/- mice caused severe retinal damage, did mice expressed a not induce the emergence of Ocular autoantigen regulatory immunity in the spleen, and the MC5r-/- classical memory Immune response when reimmunized with Ocular autoantigen. There was expression of MC5r in retinal pigment epithelial cells, in the ganglion cell and neural outer plexiform layers of healthy wild type mice retinas. The recovery of the Ocular microenvironment from EAU was not dependent on the expression of MC5r, nor was the recovery dependent on the induction of CD4+ regulatory T cells (Treg cells) in the spleen. However, protection of the retina from the inflammatory damage of EAU and the induction of Ocular autoantigen-responsive CD4+ Treg cells in the post EAU spleen requires expression of MC5r.
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Neuroimmunomodulation and Immune Privilege: the role of neuropeptides in Ocular immunosuppression.
Neuroimmunomodulation, 2002Co-Authors: Andrew W. TaylorAbstract:Regional immunoregulatory mechanisms insure that the most effective Immune defense mounted is in proportion with preserving unique tissue functionalities. Immune-Privileged tissues, such as the eye, are tissue sites of extreme regional immunoregulation. They have evolutionarily adapted several mechanisms to prevent the induction of inflammation within their tissue microenvironment. With over half a century of experimental examinations of Ocular Immune Privilege, only recently have we come to understand that neuropeptides constitutively present in Ocular tissues are part of the mechanisms of Immune Privilege.
J. Wayne Streilein - One of the best experts on this subject based on the ideXlab platform.
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Analysis of Immune Privilege in eyes with Mycobacteria tuberculosa adjuvant-induced uveitis.
Ocular immunology and inflammation, 2005Co-Authors: J. Wayne StreileinAbstract:Purpose: To examine the effects of intravitreal Mycobacteria tuberculosa adjuvant (MTA) on Ocular Immune Privilege. Methods: MTA was injected into the vitreous cavity of BALB/c mouse eyes to induce anterior uveitis. The inflamed eyes were then examined for their capacity to afford Immune Privilege to injected allogeneic tumor cells and to promote anterior chamber-associated Immune deviation (ACAID). Aqueous humor (AqH) was tested for IL-12 content and for its ability to inhibit T-cell activation. Results: AqH removed from MTA-inflamed eyes at 6 and 12 h contained high levels of IL-12, which then fell almost to baseline at 24 h. This is relevant to the finding that the inflamed eye failed to support ACAID induction at an early time period and then regained the ACAID-induction capability at a later time. Nonetheless, AqH removed from MTA-inflamed eyes retained its capacity to suppress T-cell activation, and MTA-inflamed eyes afforded extended survival to alloantigenic tumor cells implanted into the anterior...
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Ocular Immune Privilege: the eye takes a dim but practical view of immunity and inflammation.
Journal of Leukocyte Biology, 2003Co-Authors: J. Wayne StreileinAbstract:The delicate visual axis that makes pre- cise vision possible is highly vulnerable to the de- structive potential of immunogenic inflammation. Immune Privilege of the eye is the experimental expression of the way in which evolution has coped with the countermanding threats to vision of Ocular infections and Ocular immunity and inflammation. Ocular Immune Privilege has five primary features that account for its existence: blood:Ocular barri- ers, absent lymphatic drainage pathways, soluble immunomodulatory factors in aqueous humor, im- munomodulatory ligands on the surface of Ocular parenchymal cells, and indigenous, tolerance-pro- moting antigen-presenting cells (APCs). Three manifestations of Ocular Immune Privilege that have received the most extensive study are the intraOcular microenvironment, which is selectively anti-inflammatory and immunosuppressive; the prolonged acceptance of solid tissue and tumor allografts in the anterior chamber; and the induc- tion of systemic tolerance to eye-derived antigens. Anterior chamber-associated Immune deviation is known to arise when indigenous, Ocular APCs cap- ture eye-derived antigens and deliver them to the spleen where multicellular clusters of these cells, natural killer T cells, marginal zone B cells, and T cells create an antigen-presentation environment that leads to CD4 and CD8 / T cells, which as regulators, suppress induction and expression of T helper cell type 1 (Th1) and Th2 Immune expres- sion systems. The ways the eye influences local and systemic Immune responses to Ocular antigens and pathogens carry risks to and benefits for mamma- lian organisms. As loss of sight is a powerful, neg- ative-selecting force, the benefits of Ocular Immune Privilege outweigh the risks. J. Leukoc. Biol. 74: 179-185; 2003.
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Ocular Immune Privilege and the impact of intraOcular inflammation.
DNA and Cell Biology, 2002Co-Authors: J. Wayne Streilein, Jun Song Mo, Kouichi Ohta, A W TaylorAbstract:Immune Privilege, a characteristic of the internal compartments of the eye, is a physiologic mechanism that is designed to provide the eye with protection against pathogens while protecting the delicate visual axis from the sight-destroying potential of immunogenic inflammation. It is assumed that the presence of intraOcular inflammation is incompatible with the existence of Immune Privilege. The validity of this assumption has been tested in four animal models of intraOcular inflammation—systemic and local endotoxin-induced uveitis (EIU), mycobacterial adjuvant-induced uveitis (MAIU), and experimental autoImmune uveitis (EAU). Immune Privilege was assessed in inflamed eyes by growth of intracamerally injected allogeneic tumor cells, by the capacity to support Immune deviation following intracameral injection of antigen (ovalbumin, OVA), by assaying protein, leukocyte, and selected cytokine content of aqueous humor (AqH), and by capacity of inflamed AqH to suppress T cell activation in vitro. The results ...
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Immunobiology and Privilege of neuronal retina and pigment epithelium transplants.
Vision research, 2002Co-Authors: J. Wayne Streilein, Hartmut Wenkel, Parisa ZamiriAbstract:Despite the existence of Ocular Immune Privilege, Immune rejection may be a barrier to successful retinal transplantation. We have examined in mice the extent to which the subretinal space (SRS) is an Immune Privileged site, and whether retinal pigment epithelium and neuronal retinal tissue have properties of Immune Privileged tissues. We report that (1) The SRS is an Immune Privileged site; (2) Neonatal RPE is an Immune Privileged tissue; (3) Neuronal retina is a partially Immune Privileged tissue; and (4) Microglia within neonatal neural retina grafts promote photoreceptor differentiation, become activated, and induce sensitization of the recipient and serve as targets of Immune rejection.
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Immune Privilege persists in eyes with extreme inflammation induced by intravitreal LPS
European Journal of Immunology, 2001Co-Authors: Jun Song Mo, J. Wayne StreileinAbstract:Since Immune Privilege is believed to exist in the eye in order to suppress sight-destroying inflammation, we wondered whether eyes with intraOcular inflammation retain the Immune Privileged state. IntraOcular inflammation was induced by injection of lipopolysaccharide (LPS) into the vitreous cavity of BALB / c mouse eyes, which showed a peak in intensity at approximately 9 h. At this time point, inflamed eyes were examined for their capacity to afford Immune Privilege to injected allogeneic tumor cells, and to promote anterior chamber-associated Immune deviation (ACAID) to antigens injected locally. In addition, aqueous humor (AqH) harvested from inflamed eyes was tested for its ability to suppress T cell activation. Surprisingly, eyes with acute, intense intraOcular inflammation allowed allogeneic tumor cells to form progressively growing tumors, and these same eyes promoted ACAID. Moreover, AqH harvested from inflamed eyes strongly inhibited T cell activation. We conclude that the type of extreme, intraOcular inflammation evoked by intravitreally injected LPS fails to abolish Immune Privilege in the eye. These findings are discussed in light of the effects of other types of inflammation on the integrity of Ocular Immune Privilege, and with respect to the capacity of the eye to maintain Immune Privilege by more than one mechanism.
