实验性自身免疫性葡萄膜视网膜炎大鼠T细胞受体Vβ8.3基因的表达

目的 探讨实验性自身免疫性葡萄膜视网膜炎(EAU)大鼠CD4⁺T细胞抗原受体(TCR)Vβ8.3基因的表达。 方法 Lewis大鼠18只分为EAU、Freund完全佐剂及空白对照组。用Fmoc 化学合成法合成光感受器间维生素A类结合蛋白（IRBP）R16多肽片段，以诱导EAU动物模型。利用磁吸附细胞分选法(MACS)分离大鼠脾脏CD4⁺T细胞，流式细胞术检测MACS分选前后CD4⁺T细胞比例，监测细胞分选效果。通过荧光定量-聚合酶链反应法检测大鼠脾脏CD4⁺T细胞的TCR Vβ8.3基因片段的表达。 结果 IRBP R16 免疫Lewis大鼠稳定地诱导出EAU动物模型；MACS分选CD4⁺T细胞的纯度较分选前明显增高 （P＜0.001）；IRBP R16 诱导的EAU大鼠CD4⁺T细胞受体Vβ8.3基因的表达显著高于空白对照组（P＜0.05）。 结论 在IRBP R16 诱导的EAU中存在着抗原特异性T细胞受体Vβ8.3基因的优势利用，为EAU的免疫治疗提供了新的思路。 （中华眼底病杂志，2004，20：167-167）     

过继转发IRBP致敏脾细胞诱发EAU、EAP的实验研究

将光感受器间维生素A类结合蛋白(IRBP)免疫鼠的脾细胞单独或与IRBP一起培养后注射至6只Lewis鼠的腹腔内(每鼠3×10⁷个细胞),发现经IRBP刺激的脾细胞既可转移特异性免疫反应，又可使受鼠发生实验性自身免疫性葡萄膜视网膜(EAU)、实验性自身免疫性松果体炎(EAP)；而未用IRBP刺激的脾细胞则不能诱发EAU、EAP和特异性免疫反应。此结果表明细胞免疫在EAU、EAP发生中起决定性作用，并证明过继转移前用特异性抗原刺激是不可缺少的。 （中华眼底病杂志，1993，9：210-213）     

大鼠自身免疫性葡萄膜视网膜炎眼部细胞因子信号抑制因子的表达

目的:大鼠自身免疫性葡萄膜视网膜炎(experimentalautoimmune uveoretinitis,EAU)大鼠模型眼部研究细胞因子信号抑制因子(suppressor of cytokine signaling,SOCS)的表达。方法:用光感受器间维生素A类结合蛋白(interphotoreceptorretinoid-binding protein,IRBP)免疫Lewis鼠160只后,在眼组织切片上应用SOCS多克隆抗体进行免疫组织化学染色,观察其在眼组织中的表达并与正常大鼠40只做对照。结果:用IRBP免疫Lewis鼠后,免疫组织化学染色发现在虹膜、睫状体和视网膜部位可见SOCS-1和SOCS-5蛋白表达;而在正常Lewis鼠未见SOCS蛋白表达。统计学结果显示,SOCS-1和SOCS-5蛋白表达与EAU严重程度呈正相关(r1=0.954,r2=0.963,P<0.01)。结论:自身免疫性葡萄膜视网膜炎Lewis鼠出现SOCS阳性表达细胞在EAU的发病过程中起了一定的作用。     

IRBP免疫鼠血清特异性抗体的测定及动态变化

我们首次在国内提纯了光感受器间维生素 A类结合蛋白(interphotoreceptor retinoid-binding protein,IRBP),将其免疫 Lewis 大鼠后动态测定了鼠血清抗IRBP 抗体和抗视网膜 S 抗原抗体.发现抗 IRBP 抗体于免疫后第7天出现,以后逐渐上升,于第26天达高峰,未测出抗 S 抗原抗体.根据特异性抗体与实验性自身免疫性葡萄膜视网膜炎(experimental autoimmune uveoretinitis,EAU)之间的关系,讨论了特异性体液免疫反应在 EAU发生中的作用.     

实验性自身免疫性葡萄膜视网膜炎中T-bet的表达及意义

目的 研究实验性自身免疫性葡萄膜视网膜炎（EAU）中T-bet的表达及意义 方法 Lewis大鼠28只，用视网膜S抗原与Freund完全佐剂免疫24只大鼠以诱导EAU模型，另外4只作为正常对照。免疫组大鼠分别于免疫后7、12、15、21 d被处死，取所有大鼠的眼球和脾脏，固定后制作眼组织平片和眼球及脾脏的石蜡连续切片。使用单克隆抗T-bet 和CD4的抗体，通过免疫组织化学细菌蛋白过氧化物酶法在上述组织平片及切片上进行免疫组织化学单染和双染色，在光学显微镜下观察并计数阳性细胞，数据经SPSS 11.0统计学软件分析。 结果 正常眼和脾组织中均见少量T-bet阳性细胞；免疫后7 d，虹膜、视网膜及脾脏中T-bet的表达增加，免疫后15 d达高峰，免疫后21 d表达降低，但仍高于正常组。免疫组织化学双染色显示，T-bet阳性细胞中多数为CD4+。 结论 T-bet在EAU的发病中起着重要作用，其作用可能是通过激活辅助性T淋巴细胞1而实现的。（中华眼底病杂志，2004，20：172-174）     

IRBPR16多肽的合成及其致葡萄膜视网膜炎活性的探讨

目的 探讨光感受器间维生素A类结合蛋白（IRBP）的R16多肽片段的致葡萄膜视网膜炎活性。设计实验研究。研究对象36只Lewis大鼠。方法应用Fmoc法合成并纯化牛IRBPR16多肽片段,以诱导实验性自身免疫性葡萄膜视网膜炎（EAU）模型,并对该模型进行临床观察和组织学检查。培养EAU大鼠的引流淋巴结细胞,测定淋巴细胞增殖反应。各实验同时建立单纯弗式完全佐剂（CFA）免疫组和空白对照组。主要指标多肽分析,视网膜形态学,淋巴细胞增殖反应。结果合成的IRBPR16多肽片段纯度为95．6％。应用IRBPR16多肽片段作为抗原免疫Lewis大鼠,可成功诱导出EAU模型。EAU的临床分级为（3．33±0．52）级,病理分级为（3．67±0．92）级;CFA组和空白对照组大鼠眼部均无异常改变。EAU组大鼠引流淋巴结中抗原特异性淋巴细胞增殖反应增强,为（33．27±7．24）×10^cpm,显著高于CFA组[（1．91±1．16）×10^3cpm]和空白对照组[（1．23±0．51）×10^3cpm]（P〈0．05）。结论IRBPR16多肽片段具有较强的致葡萄膜视网膜炎活性,引流淋巴结抗原特异性淋巴细胞增殖反应增强。IRBPR16多肽诱导的EAU为研究人类葡萄膜视网膜炎提供了一个重要的动物模型。     

IL-17在实验性自身免疫性葡萄膜炎大鼠模型眼部的表达

目的研究IL-17阳性细胞在实验性自身免疫性葡萄膜炎（EAU）大鼠模型眼部的表达。方法用光感受器间维生素A类结合蛋白（IRBP）和氟氏完全佐剂等量混合注射于20只Lewis大鼠的右后足底部为实验组,于建模后第7、10、11、12、13、14、21、28天用裂隙灯显微镜进行眼前节检查,并根据de Smet的标准对炎症进行分级。用0.3 mL肝素（5 000 U/mL）注射至左心室以抗凝血,然后取眼球制作冰冻切片。免疫组织化学染色观察IL-17多克隆抗体在眼组织中的表达,5只正常Lewis大鼠作为对照。结果用IRBP免疫Lewis鼠后第10天,裂隙灯显微镜下可见眼前节炎症表现,免疫后第7、14、21、28天各组大鼠眼部炎症平均得分为0.4、3.2、1.6和0.2。实验组大鼠眼组织切片的苏木精-伊红染色可见炎性细胞浸润和光感受器细胞破坏。免疫组织化学染色发现,实验组虹膜、睫状体和视网膜部位可见IL-17蛋白表达,而正常组未见IL-17蛋白表达。第7、14、21、28天各组大鼠眼部组织切片染色的平均得分分别为0.6、4、2、0.4。EAU大鼠眼部炎症表现的严重程度与IL-17的表达量呈正相关（r=0.968,P〈0.01）。结论IL-17蛋白在Lewis大鼠EAU模型中呈高表达,表明IL-17阳性表达细胞在EAU的发病过程中起一定作用。     

大鼠的实验性自身免疫性葡萄膜视网膜炎的免疫致病机理

为了了解实验性自身免疫性葡萄膜视网膜炎(EAU)免疫致病机理,用Lewis鼠研究T淋巴细胞和肥大细胞的作用。用致敏的淋巴细胞特别是辅助性/诱异性T细胞亚群成功地转移给首次用来作实验的同系大鼠。接受了对S抗原致敏了的辅助性/诱导性T细胞的实验性自身免疫性葡萄膜视网膜炎(EAU)的大鼠充分表现了对此抗原的迟发型皮肤超敏反应但极轻微的Arthus反应。分析了环孢霉素、环磷酰胺,地塞米松等免疫抑制剂药物对S抗原免疫的鼠产生EAU的作用。通过选择性抑制对S抗原的迟发型皮肤超敏反应,说明仅有环孢霉素能完全抑制EAU的发生。这些资料说明T淋巴细胞在EAU致病机理中起主要的作用。根据在疾病发作以前,脉络膜的肥大细胞发生脱颗粒作用,说明除了淋巴细胞参与以外,脉络膜的肥大细胞也起了附带作用。     

Th1、Th17细胞对小鼠视网膜星形细胞的杀伤作用

背景 C57BL/6及B10RⅢ小鼠是实验性自身免疫性葡萄膜炎(EAU)动物模型常用的小鼠种系,其中C57B L/6小鼠免疫后眼部炎症较轻,而B10RⅢ小鼠免疫后眼部表现为典型的后葡萄膜炎病理改变.目的 观察培养的光感受器间维生素A类结合蛋白(IRBP)抗原特异性Th1、Th17细胞对小鼠视网膜星形细胞的杀伤作用,研究EAU中Th1及Th17细胞的致病机制. 方法 选取C57BL/6小鼠、B10RⅢ小鼠各10只,尾根部及躯干皮下注射200 μl含有200 μg IRBP1-20或IRBP161-180抗原及完全弗氏佐剂(CFA)的乳化液,共均匀注射6个点以免疫动物.流式细胞仪分析B10RⅢ小鼠模型的眼内浸润T细胞类别.分离培养C57BL/6小鼠淋巴结及脾脏IRBP特异性T细胞,分别加入白细胞介素2(IL-2)或IL-23以适于Th1、Th17细胞生长.将培养至第5天的Th1、Th17细胞分别加入到经干扰素-γ(IFN-γ)预处理的单层视网膜星形细胞中,观察细胞间的相互作用,检测肿瘤坏死因子-α( TNF-α)的质量浓度. 结果 B10RⅢ小鼠EAU模型眼球中有大量炎性细胞浸润,流式细胞仪检测证实含有IFN-γ+、IL-17+细胞和CD45+细胞,分别占9.5％、5.1％和41.4％.IRBP1-20刺激后6d,含IL-2和IL-23培养基中IFN-γ+细胞分别为44.0％、8.0％,IL17+细胞分别为1.0％、26.0％.Th1、Th17与视网膜星形细胞相互作用24 h后,可见视网膜星形细胞死亡脱落,Th17较Th1具有更强的杀伤作用.Th1、Th17细胞分别与星形细胞共培养48 h,两种培养基中TNF-α的质量浓度分别为(500±10)、(801±24) μg/L,差异有统计学意义(t=-20.36,P=0.00).结论 Th1、Th17对视网膜星形细胞均有杀伤作用,Th17细胞杀伤作用更强,在葡萄膜炎致病过程中发挥更重要的作用.杀伤过程中既有细胞直接接触作用,又有通过细胞因子介导的间接作用.     

自然杀伤T细胞结膜下注射防治大鼠角膜移植免疫排斥反应的初步研究

目的探讨自然杀伤T细胞(NKT)对大鼠角膜移植免疫排斥反应的防治作用。设计实验性研究。研究对象8只Fisher344大鼠为供体,16只Lewis大鼠为受体。方法无菌取Lewis大鼠脾脏中淋巴细胞,RPMI1640培养基体外培养三周后,流式细胞仪分选出NKT细胞(浓度5×10~4/ml)。取8只Fisher344大鼠为供体,16只Lewis大鼠为受体行穿透性角膜移植术。将受体大鼠随机分为治疗组和对照组,每组各8只。治疗组在手术结束时结膜下注射0.1ml上述浓度的NKT细胞,对照组注射相同体积生理盐水。术后观察记录植片的存活情况,术后第10天,每组2只大鼠取材,行组织病理学、免疫组织化学和流式细胞仪检测。主要指标角膜植片平均存活时间,组织病理学及免疫组织化学染色检查淋巴细胞浸润情况。结果对照组角膜植片平均存活时间为(8.00±1.58)天,NKT细胞治疗组为(26.00±1.34)天。组织病理学检查可见对照组大鼠角膜植片重度水肿,角膜基质纤维板层排列紊乱,大量炎性细胞浸润,新生血管长入植片。而治疗组植片仅表现为轻度水肿,少量炎性细胞浸润。免疫组织化学染色可见对照组植片中大量CD4 和CD8 淋巴细胞浸润,治疗组中仅见少量CD4 和CD8 淋巴细胞浸润。流式细胞仪检查结果表明在治疗组脾脏中NKT细胞为(3.90±0.32)%,明显高于对照组(1.85±0.21)%;外周血中治疗组NKT细胞为(1.34±0.12)%,对照组为(3.59±0.23)%。结论NKT细胞结膜下注射可延长角膜移植片存活时间,为防治角膜移植免疫排斥反应提供新的思路。     

Macrophages and dendritic cells in IRBP-induced experimental autoimmune uveoretinitis in B10RIII mice

PURPOSE: To investigate the characteristics of the mononuclear cell infiltrate in murine experimental autoimmune uveoretinitis (EAU). METHODS: EAU was induced by immunization with bovine interphotoreceptor retinal binding protein (IRBP) in Freund's complete adjuvant (subcutaneous injection) and pertussis toxin (intraperitoneal injection) in B10RIII mouse. Then animals were killed on days 7, 9, 12, 15, 20, 26, and 39 after immunization. Eyes were processed for hematoxylin and eosin staining to characterize the disease and to assess the severity and extent of the EAU. Single and dual immunohistochemical staining in various combinations with monoclonal antibodies against CD45, CD4, CD8, major histocompatibility complex (MHC) class II, CD11c, NLDC-145, and a variety of macrophage markers was performed. RESULTS: The authors' results showed that vitritis, vasculitis and perivasculitis, retinal detachment, and granuloma formation in retina and choroid were the predominant features of IRBP-induced B10RIII mice EAU. Immunohistologic results showed that CD4+ T cells and macrophages were the main infiltrating cells in retina and choroid throughout the entire course of the disease. MHC class II negative macrophages expressing antigens reacting with MOMA-2, F4/80, sialoadhesin, and CD11b were prominent during the peak phase of tissue damage in the retina and choroid. Dendritic cells (DCs) characterized by dual positivity for MHC class II and CD11c and negative for sialoadhesin appeared at time of disease onset and continued to be recruited during the inflammatory process. DCs at the site of inflammation were NLDC-145 weak and CD8 negative, indicating that they were of the myeloid rather than the lymphoid lineage. CONCLUSIONS: The results suggest that EAU in B10RIII mice is initiated by local-infiltrating, dendritic antigen-presenting cells, whereas tissue damage is associated with sialoadhesin-positive, phagocytic nonantigen-presenting macrophages during the effector stage.     

抗肿瘤坏死因子-α单克隆抗体治疗实验性自身免疫性葡萄膜视网膜炎的研究

目的 观察抗肿瘤坏死因子-α单克隆抗体（TNF-α MCAb）对于实验性自身免疫性葡萄膜视网膜炎（EAU）的治疗作用。方法 合成光感受器间维生素A类结合蛋白（IRBP）R16多肽片段，联合免疫佐剂诱导EAU动物模型。按照注射次数不同将大鼠分为2组，分别于IRBP R16免疫后的第6天和第4、6、8天自大鼠尾静脉注入TNF-α MCAb，裂隙灯显微镜观察其眼部临床表现，同时设未治疗组大鼠作为对照。于IRBP R16免疫后第13天测量迟发型超敏反应（DTH），并于第14天处死大鼠，取眼球行组织病理检查。应用酶联免疫吸附试验（ELISA）检测抗体注射后14 d 时大鼠血清中Th1类细胞因子γ-干扰素（IFN-γ）、Th2类细胞因子白细胞介素-4（IL-4）水平以及房水中IFN-γ水平。测量引流淋巴结细胞的抗原特异性淋巴细胞增生反应。结果 TNF-αMCAb治疗组大鼠的眼部炎症较未治疗组明显减轻，病理分级下降；房水和血清中IFN-γ水平降低，血清中IL-4增高；DTH反应下降；引流淋巴结细胞对IRBP R16多肽刺激的增生反应下降，差异均有统计学意义（P＜0.01）。与单次注射相比，3次注射的治疗效果更显著（P＜0.05）。结论 TNF-αMCAb能够有效减轻EAU大鼠眼部的炎症反应和特异性细胞免疫反应，改变Th1/Th2细胞因子平衡；多次应用作用更显著。     

The purification of bovine IRBP and its uveitogenic action]

The interphotoreceptor retinoid-binding protein, IRBP, shuttles the retinoid between photoreceptor cells and the pigment epithelium. It also induces experimental autoimmune uveoretinitis (EAU). The authors first purified IRBP in China by Con A Sepharose affinity chromatography in conjunction with the purification of bovine retinal S-antigen by ion-exchange chromatography. EAU was successfully induced by injection of emulsified IRBP 50 micrograms with Freund's complete adjuvant into the footpad of Lewis rats. It was characterized by panophthalmia with severe damage to the posterior retina, and lymphocytes predominated the inflammatory infiltration that included mononuclear and polymorphonuclear cells.     

Neutrophil‐dominant experimental autoimmune uveitis in CC‐chemokine receptor 2 knockout mice

Purpose: Murine experimental autoimmune uveitis (EAU) is an animal model of human uveitis. It has been demonstrated that ocular‐infiltrating macrophages are crucial for EAU induction, and monocyte chemoattractant protein‐1 (MCP‐1) was actually upregulated in the eye. CC chemokine receptor‐2 (CCR2) is the receptor of MCP‐1, and macrophages fail to recruit particular lesions in CCR2 knockout (KO) mice. To confirm the role of macrophages in EAU, we examined EAU in CCR2 KO mice. Methods: CCR2 KO mice and wild‐type (WT) mice that had the same genetic background were immunized with human interphotoreceptor retinoid‐binding protein peptide 1–20 emulsified in complete Freund’s adjuvant. At multiple time‐points, EAU severity was evaluated based on microscopic fundus observation and histological examination. To examine the phenotype of retinal‐infiltrating cells, single cells were prepared from the eye and analysed by flow cytometry. Results: In WT mice, EAU was induced at the peak of day 16 and marked macrophage infiltration was observed. Although macrophages failed to be recruited into the eye in CCR2 KO mice, severe uveitis was induced unexpectedly. Flow cytometry and histology revealed that most of the infiltrating cells were neutrophils. We also compared the intraocular chemokine concentrations between WT mice and KO mice. Two CXC chemokine (monokine induced by interferon‐γ and interferon‐γ‐inducible protein‐10) were upregulated in KO mice. Conclusion: Interphotoreceptor retinoid‐binding protein peptide immunization caused neutrophil‐dominant uveitis in CCR2 KO mice. In the absence of macrophages, neutrophils can be alternatively recruited and can cause tissue damage.     

Th1、Th17细胞相关因子在实验性自身免疫性葡萄膜炎大鼠中的表达及作用

目的　探讨辅助性Ｔ细胞（Ｔｈｅｌｐｅｒｃｅｌｌｓ,Ｔｈ）１、Ｔｈ１７细胞相关因子在实验性自身免疫性葡萄膜炎（ｅｘｐｅｒｉｍｅｎｔａｌａｕｔｏｉｍｍｕｎｅｕｖｅｉｔｉｓ,ＥＡＵ）中的表达及作用。方法　取清洁级纯系健康雌性Ｌｅｗｉｓ大鼠４０只随机分为ＥＡＵ组（３２只）和对照组（８只）,ＥＡＵ组用光感受器间维生素Ａ类结合蛋白诱导大鼠ＥＡＵ模型,进行临床症状评分,免疫组织化学方法检测造模后视网膜内干扰素（ｉｎｆｅｒｆｅｒｏｎ,ＩＦＮ）-γ、诱导型一氧化氮合酶（ｉｎｄｕｃｉｂｌｅｎｉｔｒｉｃｏｘｉｄｅｓｙｎｔｈａｓｅ,ｉＮＯＳ）、白细胞介素（ｉｎｔｅｒｌｅｕｋｉｎｅ,ＩＬ）-１７、ＩＬ-６的表达。ＥＬＩＳＡ法对比分析房水中各细胞因子的变化情况。结果　ＥＡＵ模型建立成功;造模后第１４天,视网膜损害以外层为主,视网膜内有大量炎细胞浸润,从而导致视网膜内结构紊乱,同时在视网膜的视锥、视杆细胞层和神经节细胞层ｉＮＯＳ、ＩＬ-１７、ＩＬ-６、ＩＦＮ-γ表达,细胞阳性率分别为２９％、４８％、５２％、７３％。在ＥＡＵ发病过程中,ＩＬ-６于造模后第７天迅速升高,第１０天达到高峰;ＩＬ-１７于造模后第１４天达到最高值,变化趋势与炎症进程一致;ＩＦＮ-γ在炎症后期仍有升高,于造模后第１６天达到最高值;ＩＬ-６、ＩＬ-１７、ＩＦＮ-γ与对照组相比,各时间点表达差异均有统计学意义（均为Ｐ＜０．０５）。ｉＮＯＳ在炎症进程中表达有所增加,但与对照组相比,各时间点的表达差异均无统计学意义（均为Ｐ＞０．０５）。结论　Ｔｈ１、Ｔｈ１７细胞相关因子调节网络共同参与实验性自身免疫性葡萄膜炎的发生发展。     

Neutralizing tumor necrosis factor-alpha activity suppresses activation of infiltrating macrophages in experimental autoimmune uveoretinitis

PURPOSE: During experimental autoimmune uveoretinitis (EAU), infiltrating macrophages become activated to express nitric oxide synthase (NOS)-2 and generate nitric oxide (NO). The current study was designed to determine whether neutralizing TNF activity with a soluble fusion protein of TNFp55 receptor (sTNFr-IgG) inhibits macrophage activation, thereby contributing to reduced tissue damage observed with such treatment. METHODS: EAU was induced in Lewis rats by active immunization with soluble retinal extract (RE) and pertussis toxin (intraperitoneally), and animals were treated on days 6 and 8 after immunization with either sTNFr-IgG or human (hu)IgG. Disease course and severity were noted clinically, and eyes were enucleated for histologic scoring, including TUNEL immunofluorescence, at various stages of disease. Infiltrating retinal macrophages were isolated through a density gradient and subsequently phenotyped by flow cytometry, analyzed for ability to produce nitrite, either spontaneously or after cytokine stimulation, and assayed by PCR for cytokine gene expression. RESULTS: Neutralizing TNF activity suppressed tissue damage without impeding myeloid cell infiltrate. Moreover, with sTNFr-IgG treatment, infiltrating macrophages demonstrated reduced nitrite production at the height of disease, and the level of apoptosis within the retina of both ED1(+) cells and resident cells was reduced. PCR analysis demonstrated a significant increase in TGF beta signal and absent or low TNF signal throughout the disease course after treatment with sTNFr-IgG. CONCLUSIONS: sTNFr-IgG successfully suppresses retinal damage and impairs macrophage activation but not trafficking during EAU. sTNFr-IgG-mediated suppression of NO production results in reduced levels of apoptosis of inflammatory cells and reduction in photoreceptor damage.     

A new procedure for experimental autoimmune uveitis with small uveitogenic peptides

PURPOSE: Demonstration of experimental autoimmune uveitis (EAU) with extremely small, fragmented peptides (12-30 amino acid residues) of interphotoreceptor retinoid-binding protein (IRPB). METHOD: Very small fragmented peptides (no. 854, 888, 907, and 1057) were conjugated to heat-killed Group A Streptococcus cells and administered as a single intravenous injection to Lewis rats. A non-uveitogenic peptide 950 was also conjugated to heat-killed Streptococcus and administered. Administration of a mixture of small peptides and Streptococcus was a control for the peptides conjugated with Streptococcus. RESULTS: The uveitogenic peptide/Streptococcus conjugates produced uveitis inflammatory responses in the uvea, retina and pineal gland. Administration of mixtures of small peptides and Streptococcus cells, and a non-uveitogenic peptide 950 conjugated with Streptococcus did not produce autoimmune uveitis. CONCLUSIONS: Since mixtures of small uveitogenic peptides and Streptococcal cells did not develop autoimmune uveitis, conjugated Streptococcal cells provided a vehicle for macrophage phagocytosos of very small uveitogenic IRBP peptides. Subsequent antigen presentation from macrophages to lymphocytes developed autoimmune uveitis. Peptide 888, one of four IRBP peptides that encompass the major uveitogenic domain, proved to be the most effective in development of uveitis.