Immunomodulation of experimental autoimmune uveoretinitis: A model of tolerance induction with retinal antigens

Dick, Andrew D.; Cheng, Y F; Liversidge, Janet; Forrester, John V.

doi:10.1038/eye.1994.10

Cited by 66 publications

(66 citation statements)

References 50 publications

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“…The inability of macrophages to produce NO under these circumstances helps explain the lack of retinal destruction in vivo. Following disease induction in murine EAU, CD4-positive IFN-␥ and TNF-␣-secreting T cells are found in the retina, this cytokine milieu classically activates infiltrating macrophages and resident microglia resulting in the production of NO (23,36,38). In TNFRp55 Ϫ/Ϫ mice, although T cells are able to infiltrate the eye during EAU, the inability of macrophages to respond to IFN-␥ leads to reduced retinal destruction.…”

Section: Discussionmentioning

confidence: 99%

“…TNFRp55 Ϫ/Ϫ and WT mice were immunized with IRBP 1-20 , as previously described (22). Mice were sacrificed on days 11, 14, 18, and 21 postimmunization, eyes were enucleated, and stained with anti-CD45 for histological disease assessment (23). The disease incidence in the TNFRp55 Ϫ/Ϫ mice (4 of 9) was significantly reduced compared with WT mice (11 of 11), implying resistance rather than suppression or a change in disease kinetics (Fig.…”

Section: ϫ/ϫ Mice Have Reduced Eau But Intact T Cell Primingmentioning

confidence: 99%

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A Selective Role for the TNF p55 Receptor in Autocrine Signaling following IFN-γ Stimulation in Experimental Autoimmune Uveoretinitis

Calder

Nicholson

Dick

2005

The Journal of Immunology

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IFN-γ stimulates macrophage activation and NO production, which leads to destruction of the retina in experimental autoimmune uveoretinitis. In this study, we investigate the mechanism of disease resistance in TNF p55 receptor-deficient animals. We show that although T cell priming is relatively unaffected, macrophages lacking the TNF p55 receptor fail to produce NO following IFN-γ stimulation because of a requirement for autocrine TNF-α signaling through the TNF p55 receptor. In contrast to the impaired activation of NO synthesis, MHC class II up-regulation was indistinguishable in wild-type and TNFRp55−/− mice stimulated with IFN-γ. These defects could be overcome by stimulating macrophages with LPS. Together, these results show that selected aspects of IFN-γ activation are controlled by autocrine secretion of TNF-α, but that this control is lost in the presence of signals generated by pathogen-associated molecular patterns recognizing receptors.

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Section: Discussionmentioning

confidence: 99%

Section: ϫ/ϫ Mice Have Reduced Eau But Intact T Cell Primingmentioning

confidence: 99%

A Selective Role for the TNF p55 Receptor in Autocrine Signaling following IFN-γ Stimulation in Experimental Autoimmune Uveoretinitis

Calder

Nicholson

Dick

2005

The Journal of Immunology

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“…were killed, and their eyes were fixed in 2.5%-buffered glutaraldehyde (Fisher Chemicals, Leics, UK) and embedded in resin for standard hematoxylin and eosin (H&E) staining. The intensity of uveoretinitis was evaluated histologically and graded using a modified version of the customized histologic grading system [23,24] by independent observers.…”

Section: Animal Modelmentioning

confidence: 99%

Reduction in shear stress, activation of the endothelium, and leukocyte priming are all required for leukocyte passage across the blood—retina barrier

Xu¹,

Manivannan

Goatman

et al. 2003

Journal of Leukocyte Biology

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The passage of leukocytes across the blood-retina barrier at the early stages of an inflammatory reaction is influenced by a complex series of interactions about which little is known. In particular, the relationship between hydrodynamic factors, such as shear stress and leukocyte velocity, to the adherence and subsequent extravasation of leukocytes into the retina is unclear. We have used a physiological method, scanning laser ophthalmoscopy, to track labeled leukocytes circulating in the retina, followed by confocal microscopy of retinal flatmounts to detect infiltrating cells at the early stage of experimental autoimmune uveitis. This has shown that retinal vessels are subjected to high shear stress under normal circumstances. During the inflammatory reaction, shear stress in retinal veins is reduced 24 h before leukocyte infiltration. This reduction is negatively correlated with leukocyte rolling and sticking in veins and postcapillary venules, the sites of leukocyte extravasation. Activation of vascular endothelial cells is also a prerequisite for leukocyte rolling and infiltration. In addition, antigen priming of leukocytes is influential at the early stage of inflammation, and this is seen clearly in the reduction in rolling velocity and adherence of the primed leukocytes in activated retinal venules, 9 days postimmunization.

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“…A number of studies have addressed the importance of CD200-mediated suppression in autoimmune uveitis [127] and uveoretinitis [49,128,129]. In one such study, an agonist monoclonal rat anti-mouse CD200R1 antibody was used to suppress IFNγ-mediated nitric oxide (NO) and interleukin-6 production.…”

Section: Regulation Of Autoimmune Disease By Cd200:cd200rmentioning

confidence: 99%

CD200:CD200R-Mediated Regulation of Immunity

Gorczynski

2012

ISRN Immunology

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The type 1 membrane glycoprotein CD200, widely expressed on multiple cells/tissues, uses a structurally similar receptor (CD200R1), whose expression is more restricted to cells of the myeloid and lymphoid lineages, to transmit signals affecting responses in multiple physiological systems. Thus CD200 expression is reported to exert effects on cancer growth, autoimmune and allergic disorders, infection, transplantation, bone development and homeostasis, and reproductive biology. It was initially thought, based on the idea that CD200R1 was mostly expressed on cells of myeloid origin, that CD200:CD200R1 interactions were primarily dedicated to controlling myeloid cell function. However additional members of the CD200R family have now also been identified, although their function(s) remain unclear, and CD200R1 itself is now known to be expressed by subsets of T cells and other cells. Together these observations add layers of complexity to our understanding of CD200-related regulation. In common with a number of physiological systems, the mechanism(s) of CD200-induced signaling seem to fit within a similar framework of opposing actions of kinases and phosphatases. This paper highlights the advances in our knowledge of immunoregulation achieved following CD200:CD200R interaction and the potential clinical applicability of that information.

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Immunomodulation of experimental autoimmune uveoretinitis: A model of tolerance induction with retinal antigens

Abstract: SUMMARY

Cited by 66 publications

References 50 publications

A Selective Role for the TNF p55 Receptor in Autocrine Signaling following IFN-γ Stimulation in Experimental Autoimmune Uveoretinitis

A Selective Role for the TNF p55 Receptor in Autocrine Signaling following IFN-γ Stimulation in Experimental Autoimmune Uveoretinitis

Reduction in shear stress, activation of the endothelium, and leukocyte priming are all required for leukocyte passage across the blood—retina barrier

CD200:CD200R-Mediated Regulation of Immunity

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