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ABSTRACT: Müller cells, the principal glial cells of the retina, play an important role in immune responses. Toll-like receptors (TLRs) are members of the pattern recognition receptor family and mediate innate and adaptive immune responses. In this study, we isolated, characterized Müller cells from mouse retina, and analyzed the expression of TLRs in these cells. We found that the mRNA of TLR2, TLR3, TLR4, and TLR5 was highly expressed by Müller cells. PAM3 and LPS, the agonists for TLR2 and TLR4, promoted Müller cells to produce the inflammatory cytokine Interleukine-6 and the chemokine MIP-2/CXCL2. These results suggest that Müller cells may be involved in innate and adaptive responses via TLR signaling in the eye. Our study should facilitate further study of the role of Müller cell in eye diseases and identification of the potential therapeutic targets.
Neurological Sciences 12/2012; · 1.32 Impact Factor
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ABSTRACT: Purpose To quantitatively evaluate aqueous flare and cells in patients with Behcet’s disease. Methods This study included 30 Behcet’s patients (52 eyes) with active uveitis. The patients were treated with immunosuppressive
agents. Aqueous flare and cells were quantified using the laser flare-cell photometry before treatment and 1 and 2months
after treatment. Result Before treatment, mean aqueous flare (ph/ms) in Behcet’s eyes was 25.7±20.5. After treatment, flare values were significantly
reduced after 1 and 2months compared with those before treatment. No significant difference was found between flare values
after 1 and 2months. Before treatment, mean cell counts (cells/0.5mm3) in Behcet’s eyes were 23.2±29.4. After treatment, cell counts were also significantly reduced after 1 and 2months compared
with those before treatment. Cell counts were further significantly reduced from 1 to 2months. Conclusion Both aqueous flare and cells were significantly increased in Behcet’s patients with active uveitis and improved after a two-month
treatment. Breakdown of the blood–aqueous barrier lasts longer than aqueous cells in these patients.
KeywordsBehcet’s disease-Aqueous flare-Aqueous cells-Blood–aqueous barrier-Laser flare-cell photometry
International Ophthalmology 04/2012; 30(5):485-489.
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ABSTRACT: To investigate the clinical features of Vogt-Koyanagi-Harada (VKH) disease presenting as acute angle closure glaucoma at onset.
Retrospective non-comparative case series.
Four hundred and eighty-six VKH patients seen from February 2001 to March 2010.
The history and clinical findings of all patients were reviewed. Auxiliary examinations, including ultrasound biomicroscopy, fundus fluorescein angiography and optical coherence tomography, were performed in certain cases. Corticosteroids with or without cyclosporine A were used to treat these patients.
Patients' demographics, clinical presentation and auxiliary examination findings.
Eight out of 486 VKH patients were misdiagnosed as acute angle closure glaucoma. The mean age of these eight patients was 55.6 years. Six patients were female. The mean intraocular pressure (IOP) at disease onset was 32.9 mmHg. All of these patients had a shallow anterior chamber and a narrow or closed angle at their first visit. The complaints of these patients were mostly headache and sudden decreased vision in both eyes. Alterations shown on ultrasound biomicroscopy included detachment of the ciliary body and peripheral choroid. The increased IOP did not respond to anti-glaucoma therapy, but resolved following treatment with corticosteroids. The eye of one patient was enucleated after failed trabeculectomies prior to referral to our uveitis centre.
VKH disease presenting with a bilateral increased IOP mostly occurs in older women. The strikingly decreased visual acuity associated with mild to moderate increased IOP is a clue to the diagnosis. The increased IOP responded well to corticosteroids but not to anti-glaucoma treatment.
Clinical and Experimental Ophthalmology 09/2011; 39(7):639-47. · 1.98 Impact Factor
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Qing Lin,
Xiao Ping Yang,
Dan Fang,
Xiangrong Ren, Hongyan Zhou,
Jiazhu Fang,
Xialin Liu,
Shiyou Zhou,
Feng Wen,
Xiaohong Yao,
Ji Ming Wang,
Shao Bo Su
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ABSTRACT: Inflammation is closely linked to angiogenesis, and Toll-like receptors (TLRs) are the key mediators of inflammatory responses. However, the impact of TLRs on angiogenesis is incompletely understood. In this study, we determined the involvement of TLRs in angiogenesis.
In a mouse model of alkali-induced corneal neovascularization (CNV), we found that CNV was attenuated in TLR4-/- but not TLR2-/- mice. Further study revealed that the absence of TLR4 led to decreased production of proangiogenic factors in association with reduced accumulation of macrophages at the site of wounds, which was associated with reduced expression of high-mobility group box-1 (HMGB1) protein, an endogenous ligand for TLR4. Topical application of HMGB1 to the injured cornea promoted CNV with increased macrophage accumulation in wild-type mice but not in TLR4-/- mice. HMGB1 treatment in vitro also promoted the production of proangiogenic factors by mouse macrophages in a TLR4-dependent manner. Furthermore, antagonists of HMGB1 and TLR4 reduced CNV and macrophage recruitment in the injured cornea of wild-type mice.
Our results suggest that the release of HMGB1 in the wounds initiates TLR4-dependent responses that contribute to neovascularization. Thus, targeting HMGB1-TLR4 signaling cascade may constitute a novel therapeutic approach to angiogenesis-related diseases.
Arteriosclerosis Thrombosis and Vascular Biology 03/2011; 31(5):1024-32. · 6.37 Impact Factor
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ABSTRACT: Viral components can trigger autoimmunity, but the involved mechanisms remain to be elucidated. Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (dsRNA) and appears to play an important role in this context. Our previous studies showed that signaling of TLR2, TLR3, TLR4 and TLR9 is highly redundant in the adjuvant effect needed to induce experimental autoimmune uveitis (EAU), an animal model of human autoimmune eye disease. In this study, we analyzed the effects of systemic delivery of polyinosinic:polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, in the induction of EAU. We found that TLR3 agonist poly(I:C) enhanced EAU scores, DTH responses and Ag-specific T cell proliferation. In addition, Ag-specific Interleukin 17 (IL-17) and interferon gamma (IFN-γ) production by draining lymph node cells was markedly increased in the poly(I:C)-treated group. Our results suggest that activation of innate immune system mediated by TLR3 signaling pathway is of importance in the pathogenesis of virus-induced autoimmune diseases.
International immunopharmacology 02/2011; 11(6):769-73. · 2.21 Impact Factor
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ABSTRACT: High-mobility group box-1 (HMGB1) plays important roles in inflammation, immune responses, and tumor progression. Since HMGB1 and its components have been shown to be mediators of a number of diseases but several sources of recombinant HMGB1 showed controversial biological activity, it is important to obtain recombinant HMGB1 with properties that resemble the native protein. For this purpose, we cloned genes coding for human HMGB1 and its active components A box and B box by PCR and inserted the cloned genes into pET28a vectors for transformation of Escherichia coli BL21. The E. coli expressed proteins were then purified with a Ni(2+)-NTA column and the endotoxin content was removed. Recombinant human HMGB1 (rhHMGB1) and its B box thus obtained stimulated, but A box inhibited, the production of the chemokine CXCL8/IL-8 by THP-1 monocytic cell line. We also used purified rhHMGB1 to immunize rabbits and generated potent anti-sera, which was capable of neutralizing the activity of rhHMGB1 in vitro and detecting the increased HMGB1 expression in inflammatory tissues in mice and humans. Thus, we have established essential means to produce biologically active rhHMGB1 that will facilitate us to study its role in diseases and to explore its potential as a therapeutic agent.
International immunopharmacology 01/2011; 11(6):646-51. · 2.21 Impact Factor
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ABSTRACT: IL-23 has been shown to be involved in the pathogenesis of Behcet's disease (BD) through promoting IL-17 production. This study examined whether IL-23R polymorphisms were associated with susceptibility to this disease in a Chinese Han population.
Four single-nucleotide polymorphisms (SNP), rs7517847, rs11209032, rs 1343151 and rs17375018 were genotyped in 338 BD patients and 407 age, sex and ethnically matched healthy controls using a PCR restriction fragment length polymorphism assay.
A significantly increased prevalence of the homozygous rs17375018 GG genotype and G allele was found in BD patients compared with controls (corrected p (p(c))<0.001,odds ratio (OR) 1.86, 95% CI 1.39 to 2.49; p(c)<0.001, OR 1.57, 95% CI 1.25 to 1.98, respectively). The frequencies of the AA genotype and A allele of the SNP rs11209032 were significantly higher in BD patients compared with controls (p(c)=0.024, OR 1.69, 95% CI 1.21 to 2.35; p(c)<0.001, OR 1.48, 95% CI 1.21 to 1.82, respectively). In addition, the results showed a significantly decreased frequency of the AGCG haplotype in BD patients compared with controls (p(c)=0.0016, OR 0.59, 95% CI 0.45 to 0.77).
This study, for the first time, identified a strong association of an SNP of IL-23R, rs17375018, with BD. The results also suggested that both rs11209032 AA and rs17375018 GG of IL-23R are predisposing genotypes for BD and that the AGCG haplotype may provide protection against BD.
Annals of the rheumatic diseases 04/2010; 69(7):1325-8. · 8.11 Impact Factor
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ABSTRACT: Polymorphisms of interleukin-23 receptor (IL23R) gene have recently been reported to be associated with the susceptibility to several immune-related diseases. The aim of this study was to determine the association of IL23R polymorphisms with Vogt-Koyanagi-Harada (VKH) syndrome, a disease presumably mediated by autoimmune response. A total of 382 Chinese Han patients with VKH syndrome and 407 healthy controls were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Data were analyzed by chi(2) analysis. All genotype distributions in healthy controls were in Hardy-Weinberg equilibrium. There was no difference among the investigated four single nucleotide polymorphisms concerning the linkage disequilibrium between the tested samples and those available in the international HapMap. The genotype and allele frequencies of rs17375018, rs7517847, rs11209032, and rs1343151 were not different between patients with VKH syndrome and healthy controls. Analysis according to gender and clinical findings did not show any association of the four polymorphisms with these parameters. In conclusion, the tested IL23R gene polymorphisms are not associated with the susceptibility to VKH syndrome in the Chinese Han population.
Human immunology 04/2010; 71(4):414-7. · 2.55 Impact Factor
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ABSTRACT: The aim of the study was to investigate the association of polymorphisms of the interleukin-23 receptor (IL23R) gene with Fuchs' syndrome in a Chinese Han population.
Three single-nucleotide polymorphisms (SNPs), rs7517847, rs11209032 and rs17375018 of IL23R were genotyped in 138 Chinese Han patients with Fuchs' syndrome and 407 healthy controls by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data were analyzed by χ(2) analysis.
All genotype and allele distributions in patients with Fuchs' syndrome and healthy controls were in Hardy-Weinberg equilibrium. The frequency of the rs11209032 AA genotype was significantly increased in patients with Fuchs' syndrome as compared to controls (corrected p [pc]=0.036, OR 1.86, 95%CI 1.21 to 2.86). There were no statistically significant differences between patients and healthy controls concerning the other two tested SNPs (rs17375018 and rs7517847). The haplotypes of the tested SNPs were not different between patients and controls. Additionally, analysis according to gender did not show any influence of sex on the association of IL23R with Fuchs' syndrome.
Our results suggested that the rs11209032 AA genotype of the IL23R gene may predispose for Fuchs' syndrome in Chinese patients.
Molecular vision 01/2010; 16:2585-9. · 2.20 Impact Factor
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ABSTRACT: To investigate the role of Foxp3-positive regulatory T cells in the development of experimental autoimmune uveoretinitis (EAU).
B10RIII mice were immunized with 50 microg IRBP(161-180) in complete Freund's adjuvant (CFA) to induce EAU. EAU was evaluated clinically and pathologically on days 0, 7, 14, 21, and 28. Foxp3 mRNA levels were detected using reverse transcription-PCR (RT-PCR) and the frequencies of CD4(+)Foxp3(+) T cells and CD4(+)CD25(+)Foxp3(+) T cells in splenocytes were assessed by flow cytometry at the aforementioned time points.
The first clinical signs of EAU were observed on day 8-9, worsened up to day 14, and then gradually resolved. Histopathologic results showed that inflammatory signs occurred on day 7, reached their peak on day 14, and then gradually decreased. The levels of Foxp3 mRNA and the frequencies of CD4(+)Foxp3(+) T cells and CD4(+)CD25(+)Foxp3(+) T cells in splenocytes increased on day 7, reached a peak on day 14, and then maintained at a high level until day 28.
An upregulation of Foxp3 expression is induced in EAU and paralleled with disease activity, suggesting a role for this lymphocyte subpopulation in the regression of this experimental uveitis model.
Ocular immunology and inflammation 01/2010; 18(1):38-43. · 0.72 Impact Factor
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ABSTRACT: To investigate the role of CD4(+)CD25(+) Treg cells in the development of experimental autoimmune uveoretinitis (EAU).
EAU was induced in B10RIII mice by immunization with IRBP(161-180) in complete Freund's adjuvant and evaluated clinically and pathologically on days 0, 7, 14, 21, and 28. Lymphocytes from draining lymph nodes (LNs) were subjected to flow cytometry to analyze the frequency of CD4(+)CD25(+) Treg cells. CD4(+)CD25(+) Treg cells and CD4(+)CD25(-) T cells were separated by means of magnetic-assisted cell sorting and cocultured or crossover cultured for 3 days. Proliferation of CD4(+)CD25(-) T cells was measured using a modified MTT assay. The levels of IFN-gamma and IL-17 in the supernatants were determined by enzyme-linked immunosorbent assay.
Clinical and histopathologic results showed a severe intraocular inflammation in the immunized mice. The frequency of CD4(+)Foxp3(+) T cells and CD4(+)CD25(+)Foxp3(+) T cells in the draining LN lymphocytes was increased on day 7, reached its peak on day 14, and maintained a high level up to day 42. CD4(+)CD25(+) Treg cells obtained from mice on days 14 and 28 after immunization showed a stronger inhibitory effect on the proliferation of CD4(+)CD25(-) T cells and the production of IFN-gamma by CD4(+)CD25(-) T cells compared with those obtained from control mice. CD4(+)CD25(+) Treg cells did not affect IL-17 production. Transfer of CD4(+)CD25(+) Treg cells obtained from EAU mice was able to suppress EAU induction by IRBP(161-180) that was not observed after transfer of cells from mice that had received CFA alone, suggesting antigen specificity of the Treg response.
A significantly increased frequency and immunoregulatory action of CD4(+)CD25(+) Treg cells is associated with the development and regression of EAU, suggesting that CD4(+)CD25(+) Treg cells are induced during EAU and may be involved in its regression.
Investigative ophthalmology & visual science 09/2009; 51(1):383-9. · 3.43 Impact Factor
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ABSTRACT: Recent studies in Caucasian uveitis patients have shown an association with the -2518 A/G polymorphism of the monocyte chemoattractant protein (MCP)-1 gene. It is unknown whether this polymorphism is also associated with ocular Behçet's disease (BD) in Chinese populations. The aim of the current study was therefore to investigate the possible involvement of MCP-1 in the susceptibility to ocular BD in Chinese Han individuals. A case control association study was performed in 296 ocular BD patients and 319 geographically and age-matched healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Binary logistic regression analysis revealed a decreased frequency of the homozygous AA genotype and an increased frequency of AG genotype of the MCP-1 -2518 polymorphism in ocular BD patients compared with healthy controls, when adjusted for gender (p = 0.048, p = 0.028, respectively). However, when segregated on the basis of several clinical findings, no any association was found between this polymorphism and ocular BD. In conclusion, the present study suggests that the MCP-1 -2518 AA genotype seems to display a protective association with ocular BD, whereas the -2518 AG genotype might be a susceptible factor for ocular BD in the Chinese Han population.
Human immunology 09/2009; 71(1):79-82. · 2.55 Impact Factor
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ABSTRACT: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a key negative regulator of T lymphocytes and has been shown to be associated with a number of autoimmune diseases. The present study was performed to assess the association between CTLA-4 polymorphisms and Behçet disease (BD) in Chinese patients.
Two hundred and twenty-eight BD patients and 207 controls were analysed for four single nucleotide polymorphisms (SNPs) (-1661A/G, -318C/T, +49G/A and CT60G/A) in the CTLA-4 gene by PCR-restriction fragment length polymorphism (RFLP) analysis. The association between SNP +49A/G and BD in Chinese population as well as other ethnic groups was analysed by meta-analysis.
No association could be detected between CTLA-4 SNPs or haplotypes and BD. Also, no association was observed between CTLA-4 polymorphisms and BD subgroups, stratified by clinical features. A meta-analysis showed that there was no heterogeneity between studies (p = 0.60, I(2) = 0%) and that CTLA-4 SNP +49 was not associated with BD (overall effect: Z = 0.26, p = 0.79).
This study and a meta-analysis failed to demonstrate any association between the tested CTLA-4 polymorphisms and BD.
The British journal of ophthalmology 07/2009; 93(10):1378-81. · 2.92 Impact Factor
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ABSTRACT: Cyclosporin A (CsA) and corticosteroids are extensively used in the treatment of autoimmune diseases including Vogt-Koyanagi-Harada (VKH) syndrome. The exact immunosuppressive mechanisms of these drugs are not exactly known. Th1 and Th17 cells are important populations involved in autoimmune diseases. In this study, we investigated whether they are involved in VKH syndrome and how their function is affected by CsA and corticosteroids. The results showed that IL-17, IFN-gamma, RORgammat and T-bet were upregulated in patients with active uveitis. CsA and corticosteroids were able to downregulate all these elevated levels which correlated with the clinical improvement of the uveitis. In vitro experiments showed that CsA and dexamethasone could decrease the frequencies of Th1 and Th17 cells and inhibit IL-17 and IFN-gamma production. These data suggest that an upregulated Th1 and Th17 response is associated with active VKH syndrome. CsA and corticosteroids may exert their immunosuppressive role by downregulating Th1 and Th17 cells.
Clinical Immunology 03/2009; 131(2):333-42. · 4.05 Impact Factor
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ABSTRACT: The polymorphisms of the Fc receptor-like 3 gene (FCRL3), a novel immunoregulatory gene, have been shown to be associated with certain autoimmune diseases. This study was designed to examine whether the polymorphisms of FCRL3 are associated with susceptibility to Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese population.
A case-control study was performed in 230 Chinese VKH patients and 301 healthy controls. Four single nucleotide polymorphisms (SNPs; -169C/T, -110A/G, +358C/G, and +1381A/G) in FCRL3 were detected using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). human leukocyte antigen -DR4 (HLA-DR4) and HLA-DRw53 genotyping was performed using PCR techniques.
The results showed that the frequency of haplotype CACG was significantly lower in patients when compared with that in controls (p=0.0018, corrected p [pc]=0.0288). A significantly higher frequency was found for haplotype CGGG in HLA-DR4 negative patients than in HLA-DR4 negative controls (p=9.94 x 10(-8), Pc=1.59 x 10(-6)). There were no significant differences in the allele and genotype frequencies of the four investigated SNPs between VKH patients and controls. HLA-DR4 and HLA-DRw53 were significantly associated with VKH syndrome (p=3.21 x 10(-16) and p=7.08 x 10(-5), respectively). Stratification analysis according to HLA-DR4 and HLA-DRw53 did not show any association of FCRL3 polymorphisms with VKH syndrome.
Our study confirms the previous association of HLA-DR4 and HLA-DRw53 with VKH syndrome but fails to demonstrate an association between FCRL3 polymorphisms and VKH syndrome. Haplotype CACG might be a protective haplotype for VKH syndrome, and haplotype CGGG may be a risk haplotype in HLA-DR4 negative individuals.
Molecular vision 02/2009; 15:955-61. · 2.20 Impact Factor
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ABSTRACT: Vogt-Koyanagi-Harada (VKH) syndrome is an autoimmune disease. The monocyte chemoattractant protein-1 (MCP-1) gene has been implicated in the pathogenesis of certain autoimmune diseases. The aim of this study was to examine whether a MCP-1 polymorphism was associated with VKH syndrome.
A case-control analysis was performed using genomic DNA samples from 307 VKH patients and 319 age-, sex-, and ethnically-matched healthy controls. The MCP-1 polymorphism at the -2518 A/G locus was genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay.
The distribution of genotypic frequency of the MCP-1 -2518 A/G polymorphism in all subjects did not deviate from Hardy-Weinberg equilibrium (HWE; p>0.05). Allelic and genotypic frequency analysis revealed no significant difference between VKH patients and healthy controls for the MCP-1 -2518 A/G polymorphism (p>0.05). No significant differences were found according to gender and neither was found according to extraocular findings including neck stiffness, tinnitus, alopecia, poliosis, dysacusia, scalp hypersensitivity, and vitiligo.
The result suggests that the susceptibility to VKH syndrome in Chinese Han patients may be not influenced by the MCP-1 -2518 A/G polymorphism.
Molecular vision 02/2009; 15:1537-41. · 2.20 Impact Factor
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ABSTRACT: To analyze the potential association of programmed cell death 1 (PDCD1) with Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population.
Three single nucleotide polymorphism (SNPs), PD-1.3G/A, PD-1.5C/T, and PD-1.6G/A, were genotyped in 247 VKH patients and 289 age-, sex-, and ethnically-matched healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The associations of genotypes and alleles with VKH syndrome were analyzed.
All genotype distributions in healthy controls were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of PD-1.3, PD-1.5, and PD-1.6 were not different between patients with VKH syndrome and healthy controls. No significant difference was observed according to the status of human leukocyte antigen (HLA)-DR4 and HLA-DRw53. Compared to the controls, lower frequencies of the PD-1.5C genotype and allele frequencies were observed in VKH patients with extraocular findings.
PD-1.3 and PD-1.6 polymorphisms are not associated with the susceptibility to VKH syndrome in the Chinese Han population. However, PD-1.5 may be negatively associated with the occurrence of extraocular manifestations of VKH syndrome.
Molecular vision 02/2009; 15:386-92. · 2.20 Impact Factor
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ABSTRACT: To evaluate the effect of rapamycin (RAPA) and dexamethasone (DEX) on the production of IL-17 and IFN-gamma by peripheral blood mononuclear cells (PBMCs) from Vogt-Koyanagi-Harada (VKH) patients and healthy individuals.
Blood samples were drawn from 10 active VKH patients and 10 healthy individuals. PBMCs were cultured with or without anti-CD3 and anti-CD28 antibodies in the presence or absence of different concentrations of RAPA or DEX for 72 h. IL-17 and IFN-gamma concentrations in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA).
The expression of IL-17 and IFN-gamma was significantly increased in active VKH patients compared with that in healthy controls. Both RAPA and DEX were able to significantly inhibit the production of IL-17 and IFN-gamma by PBMCs from patients and healthy controls. RAPA was able to completely inhibit IL-17 production at a dosage of 10 ng/ml but only partially suppressed IFN-gamma production even at a much higher concentration (1000 ng/ml). DEX inhibited the production of both IL-17 and IFN-gamma by approximately 70%.
This study indicates that both RAPA and DEX inhibit the production of IL-17 and IFN-gamma by PBMCs. RAPA is much stronger in inhibiting the production of IL-17 than DEX.
The British journal of ophthalmology 12/2008; 93(2):249-53. · 2.92 Impact Factor
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ABSTRACT: Retinal S-antigen (S-Ag) is a most characterized autoantigen of autoimmune uveitis. The recognized immunodominant epitope of human S-Ag in patients with uveitis has not been identified. In this study, we selected certain patients with active uveitis to map the Th1 cell epitope spectrum of human S-Ag in Behcet's disease(BD).
Blood samples were taken from eight active BD patients who showed an immune response to 40 mixed overlapping peptides spanning the entire sequence of human S-Ag. Peripheral blood mononuclear cells were isolated and stimulated with single S-Ag peptide at 5 microg/ml or 20 microg/ml. Single-cell immune responses were measured by IFN-gamma ELIspot assay.
BD patients heterogeneously responded to the S-Ag peptides at two concentrations. In general, the responses to 5 microg/ml peptides were slightly stronger than those to 20 microg/ml peptides, while the maximum SFC frequency to single peptide at the two concentrations was similar. Several peptides including P31, P35 and P40 induced a prominent response, with the frequency of S-Ag specific cells being about 0.007%. Significant reactivity pattern shift was noted in patients with different disease courses.
Certain active BD patients have S-Ag specific Th1 cells with a low frequency. The S-Ag epitope specificity between patients is highly heterogeneous, and varies with the uveitis course.
Albrecht von Graæes Archiv für Ophthalmologie 11/2008; 247(4):555-60. · 2.17 Impact Factor
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ABSTRACT: CD8+ regulatory T cells (Treg) have been considered to be involved in a model of ocular-induced tolerance, known as anterior chamber-associated immune deviation (ACAID). The phenotype and characteristics of CD8+Treg in ACAID remain only poorly understood. Recent studies have reported that the CD94-Qa-1 system is implicated in the induction of ACAID CD8+Treg, but the functions and characteristics of CD8+CD94+T cells remain unclear.
Both mRNA and protein of CD94 and NKG2A were markedly up-regulated on splenic CD8+T cells of ACAID mice compared with controls. Flow cytometric analysis showed that very few CD8+CD94+T cells express granzyme B, perforin and Foxp3. CD8+CD94+T cells, but not CD8+CD94-T cells, magnetically isolated from the spleens of ACAID mice, produced large amounts of TGF-beta1 and exhibited suppressive activity in vitro. Neutralization of TGF-beta1 caused reversal of suppression mediated by CD8+CD94+T cells.
CD8+CD94+T cells from ACAID mice exhibited suppressive activity in association with enhanced expression of TGF-beta1, suggesting that CD8+Treg are mainly distributed in CD94+T cell subpopulations.
BMC Immunology 10/2008; 9:53. · 2.53 Impact Factor
