Pathology of experimental autoimmune uveoretinitis in mice

Chan, Chi‐Chao; Caspi, Rachel R; Ni, Ming; Leake, William C.; Wiggert, Barbara; Chader, Gerald J.; Nussenblatt, Robert B.

doi:10.1016/0896-8411(90)90144-h

Cited by 177 publications

(131 citation statements)

References 13 publications

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“…Disease severity was scored in a masked fashion after examination of four sections of each globe cut at different levels. Severity of EAU for each eye was graded on a scale of 0 (no disease) to 4 (maximum disease) in half-point increments, according to a semiquantitative system previously described (1, 37,38). Identification of retinal microvascular changes using retinal whole mounts were prepared as previously described (39).…”

Section: Histology and Retinal Mountingmentioning

confidence: 99%

Limited Peripheral T Cell Anergy Predisposes to Retinal Autoimmunity

Lambe¹,

Leung²,

Ferry³

et al. 2007

The Journal of Immunology

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Autoimmune uveoretinitis accounts for at least 10% of worldwide blindness, yet it is unclear why tolerance to retinal Ags is so fragile and, particularly, to what extent this might be due to defects in peripheral tolerance. To address this issue, we generated double-transgenic mice expressing hen egg lysozyme, under the retinal interphotoreceptor retinoid-binding promoter, and a hen egg lysozyme-specific CD4+ TCR transgene. In this manner, we have tracked autoreactive CD4+ T cells from their development in the thymus to their involvement in uveoretinitis and compared tolerogenic mechanisms induced in a variety of organs to the same self-Ag. Our findings show that central tolerance to retinal and pancreatic Ags is qualitatively similar and equally dependent on the transcriptional regulator protein AIRE. However, the lack of Ag presentation in the eye-draining lymph nodes results in a failure to induce high levels of T cell anergy. Under these circumstances, despite considerable central deletion, low levels of retinal-specific autoreactive CD4+ T cells can induce severe autoimmune disease. The relative lack of anergy induction by retinal Ags, in contrast to the same Ag in other organs, helps to explain the unique susceptibility of the eye to spontaneous and experimentally induced autoimmune disease.

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Section: Histology and Retinal Mountingmentioning

confidence: 99%

Limited Peripheral T Cell Anergy Predisposes to Retinal Autoimmunity

Lambe¹,

Leung²,

Ferry³

et al. 2007

The Journal of Immunology

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“…Sections were stained with hematoxylin and eosin. The severity of the disease was determined for each eye and scored on a scale of 0-4 in half-point increments according to a semiquantitative system described previously [42]. Briefly, monocyte infiltrations in the ciliary body, choroids, and retina were scored as 0.5; retinal perivascular infiltration and monocyte infiltration in the vitreous as 1; granuloma formation in the uvea and retina, presence of occluded retinal vasculitis along with photoreceptor folds, serous detachment and loss of photoreceptor as 2; and formation of Dalen-Fuchs nodules and development of subretinal neovascularization as 3 and 4 depending on the number and the size of the lesions.…”

Section: Induction Of Eau Mab Treatment and Assessmentmentioning

confidence: 99%

“…Complementary DNA was synthesized at 42 C for 2 h in the presence of SuperScript II RNaseH -Reverse Transcriptase and Random Primers (Invitrogen, Carlsburg, CA) in 20 lL reaction volumes. RT-PCR was conducted in a 50-lL reaction mixture using 0.5 lg of cDNA as template.…”

Section: Rt-pcr Analysis Of B7rp-1 Expressionmentioning

confidence: 99%

The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis

et al. 2006

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ICOS/B7RP-1 is a new member of the CD28/B7 family of costimulatory molecules and plays differential roles in autoimmune diseases. In this study, we examined the role of ICOS/B7RP-1 pathway in the pathogenesis of mouse experimental autoimmune uveoretinitis (EAU), an animal model of human autoimmune uveitis. ICOS expression was found on infiltrating CD4 + T cells in the region of the retina in EAU-induced mice. The anti-B7RP-1 monoclonal antibody (mAb)-treated or ICOS-deficient mice showed a substantial reduction of disease scores. Blockade of ICOS/B7RP-1 interaction during the effector phase ameliorated the disease, whereas its blockade during the induction phase exhibited no significant effect. Moreover, administration of anti-B7RP-1 mAb effectively ameliorated the disease induced by adoptive transfer of pathogenic T cells. The anti-B7RP-1 mAb treatment inhibited the expansion and/or effector function of pathogenic T cells, given that proliferative response and IFN-c production by lymph node cells were reduced upon restimulation with the antigen peptide in vitro. These results suggest that the ICOS/B7RP-1 interaction plays a critical role in the pathogenesis of uveitis. We also indicated that ICOS-mediated costimulation plays differential roles in EAU and experimental autoimmune encephalomyelitis, which is also a Th1 disease induced in the same manner as EAU.

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“…Mice simultaneously received 0.3 μg Bordetella pertussis toxin. Clinical disease was scored by fundoscopy (31) and histological analysis (32), as detailed in SI Materials and Methods. Tissue sections were also examined using a multiphoton laser-scanning confocal microscope with fluorescence emission detected with 515/30 (emerald-GFP, green) and 600/40 (mCherry, red), as described (26,31).…”

Section: Methodsmentioning

confidence: 99%

Key role for IL-21 in experimental autoimmune uveitis

Wang

Kim

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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IL-21 is a pleiotropic type 1 cytokine that shares the common cytokine receptor γ-chain, γ c , with IL-2, IL-4, IL-7, IL-9, and IL-15. IL-21 is most homologous to IL-2. These cytokines are encoded by adjacent genes, but they are functionally distinct. Whereas IL-2 promotes development of regulatory T cells and confers protection from autoimmune disease, IL-21 promotes differentiation of Th17 cells and is implicated in several autoimmune diseases, including type 1 diabetes and systemic lupus erythematosus. However, the roles of IL-21 and IL-2 in CNS autoimmune diseases such as multiple sclerosis and uveitis have been controversial. Here, we generated Il21 -mCherry/ Il2 -emGFP dual-reporter transgenic mice and showed that development of experimental autoimmune uveitis (EAU) correlated with the presence of T cells coexpressing IL-21 and IL-2 into the retina. Furthermore, Il21r −/− mice were more resistant to EAU development than wild-type mice, and adoptive transfer of Il21r −/− T cells induced much less severe EAU, underscoring the need for IL-21 in the development of this disease and suggesting that blocking IL-21/γ c –signaling pathways may provide a means for controlling CNS auto-inflammatory diseases.

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Pathology of experimental autoimmune uveoretinitis in mice

Cited by 177 publications

References 13 publications

Limited Peripheral T Cell Anergy Predisposes to Retinal Autoimmunity

Limited Peripheral T Cell Anergy Predisposes to Retinal Autoimmunity

The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis

Key role for IL-21 in experimental autoimmune uveitis

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