Nasal administration of retinal antigens maintains immunosuppression of uveoretinitis in cyclosporin-a-treated lewis rats: Future treatment of endogenous posterior uveoretinitis?

Kreutzer, B; Laliotou, Barbara; Cheng, Y F; Liversidge, Janet; Forrester, John V.; Dick, Andrew D.

doi:10.1038/eye.1997.125

Cited by 10 publications

(3 citation statements)

References 29 publications

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“…S-antigen (S-Ag), interphotoreceptor retinoid binding protein (IRBP), or retinal extract (RE; containing a mixture of these and other soluble uveitogenic antigens) induce tolerance to S-Ag, IRBP, or RE induced EAU 59 28 RE was prepared as described9 by hypotonic lysis of freshly dissected bovine retinas in the dark. S-Ag and IRBP were purified from retinal extract under aseptic conditions and filter sterilised as previously described 29.…”

Section: Methodsmentioning

confidence: 99%

Single dose intranasal administration of retinal autoantigen generates a rapid accumulation and cell activation in draining lymph node and spleen: implications for tolerance therapy

Dick

Sharma²,

Liversidge³

2001

British Journal of Ophthalmology

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Background/aims-A single intranasal delivery of retinal autoantigen suppresses eVectively experimental autoimmune uveoretinitis (EAU). To further unravel underlying mechanisms the authors wished to determine, firstly, the kinetics of antigen delivery and, secondly, the early cellular responses involved in the initial stages of nasal mucosal tolerance induction. Methods-Flow cytometry, cell proliferation assays, and microscopy were used to track antigen following a single, intranasal dose of Alexa-488 labelled retinal antigen. Results-A rapid accumulation of antigen within both superficial cervical lymph nodes (SCLN) and spleen was observed after 30 minutes. Significant proliferative responses to IRBP were elicited by 48 hours indicating that systemic priming of naive T cells to retinal antigen had occurred. Cell activation was further confirmed by immunoprecipitation studies, which demonstrated phosphorylation of STAT4 but not STAT6 in both lymph nodes and spleen. However, at 24 hours, STAT4 heterodimerisation with STAT 3 was only observed in spleen. Conclusions-The results provide novel evidence that following a single intranasal application rapid transfer of antigen occurs. Resulting T cell proliferation develops consequent to diVerential cell signalling in SCLN and spleen. Further understanding of these underlying cellular mechanisms, in particular as is inferred by the results the contribution of local versus systemic tolerance induction, may assist in strategies to clinically apply mucosal tolerance therapy successfully. (Br J Ophthalmol 2001;85:1001-1006 Models of tolerance induction via the mucosa have been shown to be eVective for the prevention of several autoimmune diseases. The eVectiveness of the treatment is dependent on parameters such as the antigen used, its dose and route of delivery, and various mechanisms have been identified, including T cell anergy, generation of regulatory Th3 (TGF producing) cells or CD8+ T cells and T cells.

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Section: Methodsmentioning

confidence: 99%

Single dose intranasal administration of retinal autoantigen generates a rapid accumulation and cell activation in draining lymph node and spleen: implications for tolerance therapy

Dick

Sharma²,

Liversidge³

2001

British Journal of Ophthalmology

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“…A later report 14 suggested that peripheral tolerance could still be induced with a nasal tolerant even if cyclosporine was used. However, the nasal administration of antigen could not reliably suppress active disease.…”

Section: Nasal Administration Of Antigenmentioning

confidence: 99%

Orally and Nasally Induced Tolerance Studies in Ocular Inflammatory Disease: Guidance for Future Interventions

Nussenblatt

2004

Annals of the New York Academy of Sciences

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The induction of both oral and nasal tolerance has been used in both experimental models of ocular disease and clinically. Initial work centered around the abrogation of experimental autoimmune uveitis using either one or two whole uveitogenic antigens. Other models of ocular disease have included a corneal transplant model, demonstrating that feeding splenocytes from the donor strain of rats enhanced corneal engraftment. Fragments of pertinent antigens have been shown to alter the expression of experimental uveitis and possibly human disease. A randomized, masked study in uveitis provided valuable information for future studies, demonstrating that single antigen feeding provided far better protection than the feeding of multiple antigens. This review will deal with animal and human studies in the treatment of ocular inflammatory disease with the goal of extracting from past experience how to construct a future study in humans.

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“…tolerance that involves regulatory cells and is therefore transferable into nontolerant recipients. In adoptive transfer experiments, T cells from donors given autoantigen via mucosal routes are able to suppress the development of autoimmune diseases including diabetes in the nonobese diabetic mouse [17,22±26], experimental autoimmune encephalomyelitis in rats and mice [27±29], collagen-induced arthritis [27] and experimental uveoretinitis [30,31].…”

Section: Mechanisms Of Mucosal Tolerancementioning

confidence: 99%

Prevention of Autoimmune Type 1 Diabetes via Mucosal Tolerance: Is Mucosal Autoantigen Administration As Safe and Effective As It Should?

Hänninen

2000

Scand J Immunol

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Mucosal immune response to an antigen leads to a state of attenuated systemic response to the same antigen, known as mucosal or oral tolerance. Thus, autoantigen administration via mucosal routes could be useful in the prevention of autoimmune diseases. Although in various models of autoimmune disease it is often effective, in some cases it is ineffective and in other cases even harmful. In these cases it is likely that, concomitantly with tolerance, a productive immune response is induced that exacerbates autoimmunity. Recent evidence suggests that induction of cytotoxic T lymphocytes capable of destroying pancreatic beta cells may be an unavoidable consequence of mucosal administration of pancreatic beta-cell associated autoantigen. To improve the safety and efficacy of mucosal tolerance induction in the prevention of type 1 diabetes, further means to control the induction of cytotoxic T lymphocytes and other potentially tissue-destructive immune effectors may be required.

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Nasal administration of retinal antigens maintains immunosuppression of uveoretinitis in cyclosporin-a-treated lewis rats: Future treatment of endogenous posterior uveoretinitis?

Cited by 10 publications

References 29 publications

Single dose intranasal administration of retinal autoantigen generates a rapid accumulation and cell activation in draining lymph node and spleen: implications for tolerance therapy

Single dose intranasal administration of retinal autoantigen generates a rapid accumulation and cell activation in draining lymph node and spleen: implications for tolerance therapy

Orally and Nasally Induced Tolerance Studies in Ocular Inflammatory Disease: Guidance for Future Interventions

Prevention of Autoimmune Type 1 Diabetes via Mucosal Tolerance: Is Mucosal Autoantigen Administration As Safe and Effective As It Should?

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