大鼠烟曲霉菌性角膜炎角膜局部的免疫学研究

目的探讨大鼠角膜真菌感染后角膜局部的免疫反应机制。方法模拟角膜外伤制作大鼠的烟曲霉菌性角膜炎模型，在感染后不同阶段进行病理切片和免疫组化观察角膜局部中性粒细胞、总T淋巴细胞及T淋巴细胞亚群、树突状细胞、B淋巴细胞的动态变化。结果在大鼠烟曲霉菌性角膜炎早期，见大量中性粒细胞及少量CD3^＋T、CD4^＋T、CD8^＋T淋巴细胞和LC浸润，未检测到B淋巴细胞。中期，中性粒细胞浸润达高峰，T淋巴细胞浸润增加，其中CD4^＋T淋巴细胞多于CD8^＋T淋巴细胞。树突状细胞亦增多，B淋巴细胞开始出现。晚期，中性粒细胞数目有所减少，T淋巴细胞浸润达高峰，CD4^＋T淋巴细胞亦多于CD8^＋T淋巴细胞，B淋巴细胞少量表达。结论免疫反应与真菌性角膜炎的病程变化有密切的关系。     

角膜碱烧伤后机体巨噬细胞和淋巴细胞的功能变化

目的了解并动态观察角膜碱烧伤后机体巨噬细胞的功能状况和淋巴细胞的免疫水平。方法新西兰兔单眼Ⅱ度角膜碱烧伤,于烧伤前和后第1、3、5、7、9周分别获取实验兔腹腔巨噬细胞和外周血淋巴细胞,以落片法进行巨噬细胞吞噬鸡红细胞试验,并应用3H—TdR掺入法进行淋巴细胞转化功能检测。结果角膜碱烧伤后,巨噬细胞体积增大,吞噬活跃,内消化力增强;吞噬率和吞噬指数明显升高(P<0.05)。淋巴细胞对植物血凝素(PHA)和特异性的烧伤角膜蛋白刺激具有显著的应答反应(P<0.05)。结论角膜碱烧伤可致机体巨噬细胞活性显著增强,T淋巴细胞处于致敏状态,对促分裂原刺激有较强应答反应。说明细胞免疫参与了角膜碱烧伤后的病理过程。     

CD28/CTLA4-B7协同刺激分子与角膜移植免疫

角膜移植排斥反应是移植失败的主要原因。致敏T淋巴细胞在角膜移植排斥反应中起着重要的作用，是角膜排斥过程中的主要效应细胞。而T淋巴细胞的激活需要两个信号刺激，即除了通过APC递呈MHC处理过的抗原给抗原特异性T细胞提供第1信号外，还需协同刺激分子作为辅助信号的协同作用。才能使T细胞产生正常的免疫应答。如果缺少协同刺激分子的第2信号，将会导致调节性T细胞的无反应性或特异性免疫耐受。[眼科新进展2005；25（5）：476—478]     

厌氧菌性角膜炎致病机制的实验研究

目的观察厌氧菌性角膜炎的临床特征及病理改变,探讨其致病机制。设计实验性研究。研究对象健康成年新西兰白兔25只。方法新西兰白兔按每组5只,随机分为5组,每组随机选取1只作为对照。向实验组的兔右眼角膜基质内分别注射痤疮丙酸杆菌悬液,建立动物模型,对照组注射生理盐水。分别于建模后5、8、12、17、23天进行临床表现评分,并取术眼角膜,分别进行角膜厌氧菌培养、组织病理学观察、CD4 /CD8 T淋巴细胞免疫组化染色及ELISA方法测定TNF-α、IL-8含量。主要指标组织病理学改变、CD4 /CD8 T淋巴细胞表达、TNF-α及IL-8含量。结果兔厌氧菌性角膜炎主要表现为局限性角膜基质浸润,伴有周围组织水肿,后期出现角膜新生血管。炎症细胞以嗜酸性粒细胞为主,在第8天和第17天出现两个峰值(500.0±164.3和665.0±28.1);单核细胞及淋巴细胞数量在第17天分别增加至118.0±17.2及60.5±13.0。角膜组织内CD4 、CD8 T淋巴细胞表达呈阳性,CD4 表达持续强于CD8 表达。角膜内TNF-α及IL-8含量在第5、12、17天分别为(21.99±4.56)pg/ml和(22.39±4.20) pg/ml、(9.32±2.89)pg/ml和(8.10±7.24)pg/ml、(20.72±8.20)pg/ml和(22.48±11.33)pg/ml。结论嗜酸性粒细胞及TNF-α、IL-8参与了厌氧菌性角膜炎的炎症反应过程,T淋巴细胞介导的迟发型超敏反应具有重要作用。(眼科,2007,16:357-360)     

可溶性B、T淋巴细胞衰减因子及其配体在单纯疱疹性角膜基质炎小鼠体内的异常表达

目的 研究B、T淋巴细胞衰减因子(B and T lymphocyte attenuator,BTLA)及其配体疱疹病毒侵入介体(herpes virus entry mediator,HVEM)在单纯疱疹性角膜基质炎(herpetic stromal keratitis,HSK)小鼠角膜组织中及外周血CD4+T细胞上的表达水平,探讨共抑制信号BTLA-HVEM是否参与了CD4+T细胞介导的HSK免疫病理反应.方法 将106 PFU的单纯疱疹病毒Ⅰ型(herpes simplex virus type 1,HSV-1)KOS毒株接种于BALB/c鼠的角膜上建立HSK动物模型,分别于角膜接种病毒前(0 d),接种病毒后的第3、7、10、14、21天,用毛细管取小鼠的左眼眼眶静脉窦血1 mL,分离淋巴细胞,行荧光抗体染色,用流式细胞仪检测CD3+ CD4+ BTLA+T细胞和CD3+ CD4+ HVEM+T细胞阳性率;在裂隙灯显微镜下观察小鼠角膜变化;免疫组织化学方法检测BTLA蛋白及HVEM蛋白在角膜组织中的表达.结果 BALB/c鼠的角膜接种HSV-1后的1～5d,角膜擦拭液中均检测出HSV-1复制,表明小鼠感染了单纯疱疹病毒.裂隙灯显微镜观察显示:角膜接种HSV-1后第3天,所有小鼠均患了急性上皮性角膜炎,并于感染后1周内痊愈,自病毒接种后第8天起,小鼠出现角膜基质炎的改变,表现为角膜基质呈灰白色混浊,角膜基质混浊于病毒接种后的第10天达到高峰,持续至第14天后逐渐减轻.流式细胞仪检测显示,小鼠外周血淋巴细胞中CD3+CD4+BTLA+T细胞和CD3+ CD4+ HVEM+T细胞的阳性率,在角膜接种病毒前(0 d)分别为(3.15±0.60)％和(9.84±1.06)％,在角膜接种病毒后第10天(HSK疾病程度最严重时)分别增加到(20.47±3.15)％和(45.18±3.90)％(与0d相比差异均有显著统计学意义,均为P＜0.01).免疫组织化学方法检查HSK小鼠角膜组织中BTLA和HVEM的蛋白表达结果一致:HSK临床表现最严重时,即病毒接种后第10天时,BTLA蛋白和HVEM蛋白在角膜组织中表达最强,主要表达于角膜基质层内浸润的炎性细胞上,角膜上皮层和内皮层也有表达.结论 在HSK小鼠模型中,BTLA及其配体HVEM蛋白在角膜组织中及外周血CD4+T细胞上表达明显增强,共抑制信号BTLA-HVEM参与了CD4+T细胞介导的HSK的免疫病理过程.     

单纯疱疹性角膜炎几种常用辅助诊断方法的比较

目的 比较常用的3种检测单纯疱疹性角膜炎(HSK)辅助诊断方法的敏感性和临床实用性。方法6只新西兰白兔双眼接种1×105PFU单纯疱疹病毒I型(HSV-I)McKrea株。病毒接种后第8天应用无环鸟苷眼膏每2 h 1次,共4次。另外2只兔中1只兔双眼在角膜上划痕但不接种病毒,另1只兔双眼角膜接种曲霉菌作为阴性对照。在病毒接种后的3、9、21天,利用病毒分离、多聚酶链反应(PCR)和蛋白吸附膜快速单纯疱疹病毒I型抗原检测方法进行检测。结果 接种后第2天全部角膜出现典型的HSK点状或树枝状浸润,第5天出现地图状溃疡,第21天仍有2只角膜有持续性感染。抗病毒治疗1天后无明显好转。2只兔于接种后14和16天死亡。病毒分离方法只有接种后3天的泪液培养阳性,第9、21天的标本检测均为阴性。有11/12、11/12和6/8只角膜在接种后的第3、9、21天用PCR方法检测到了HSV-I DNA。蛋白吸附膜抗原检测在接种后的第3、9、21天的阳性率分别为12/12、12/12和3/8。结论 蛋白吸附膜快速HSV—I检测是一种快速、简便、经济的方法。其阳性结果与临床表现相吻合。     

大鼠烟曲霉菌性角膜炎角膜局部细胞间黏附分子-1的表达及其与局部炎症反应的关系

目的探讨大鼠角膜真菌感染后角膜局部细胞间黏附分子-1(ICAM-1)的表达及其与局部炎症反应的关系。设计实验研究。研究对象烟曲霉菌感染后的大鼠角膜。方法各组大鼠左眼为实验眼,右眼为对照眼。在建模后早期(1~3天)、中期(4~7天)、晚期(10~14天)三个不同阶段取下角膜组织,采用逆转录聚合酶链式反应(RT-PCR)检测ICAM-1在不同病程角膜组织中的表达。应用免疫组化及HE染色的方法,观察不同病程角膜组织中中性粒细胞、总T淋巴细胞的动态变化。主要指标ICAM-1及中性粒细胞、总T淋巴细胞。结果 ICAM-1早期开始表达(0.58±0.21),中期达高峰(1.22±0.12),至晚期时仍有少量表达(0.94±0.07)。这一变化趋势与角膜局部中性粒细胞的变化一致。总T淋巴细胞在病程中逐渐增多,病程后期达高峰。ICAM-1的表达在实验对照组与实验组早、中、晚期组四组间差异均有统计学意义(P均=0.000)。结论 ICAM-1参与了角膜烟曲霉菌性感染后角膜局部的炎症反应。     

角膜表面镜片术建立兔棘阿米巴角膜炎模型

目的建立一种理想的模拟临床人角膜棘阿米巴感染的动物模型,并对其角膜组织损伤的临床表现和组织病理学改变进行观察。方法20只新西兰大白兔利用角膜表面镜片术建立棘阿米巴角膜炎的动物模型,在角膜植片内皮面作#形划痕,用10-0尼龙缝线将其固定于受体角膜上,将棘阿米巴滋养体混悬液注入植片与植床间,建立棘阿米巴角膜炎模型,右眼为实验眼,左眼为对照眼;并在接种后第1天、第3天、第5天、第7天、第9天、第14天、第28天行裂隙灯显微镜检查及临床评分、角膜刮片湿封片镜检、角膜组织病理检查及培养。结果应用角膜表面镜片术成功建立兔眼棘阿米巴性角膜炎的动物模型,并经角膜刮片及培养、组织病理切片染色检查证实。实验眼角膜出现水肿,基质环形浸润,角膜新生血管等表现,对照眼均未见感染;实验眼病理组织切片上可见基质层内的棘阿米巴滋养体或包囊,伴有中性粒细胞、单核巨噬细胞、嗜酸性粒细胞等浸润。结论应用角膜表面镜片术建立的兔棘阿米巴角膜炎动物模型模拟了临床人角膜棘阿米巴感染过程,为研究棘阿米巴角膜炎的发病机制及临床治疗奠定了可靠的实验基础。     

单疱病毒潜伏感染的三叉神经节培养

新西兰白兔经角膜接种ＨＳＶ－１Ｍｃｋｒａｅ株后，在三叉神经节内形成潜伏感染。当接种病毒后第３０～１００天时，分别摘除ＴＧ做组织培养，在培养到第８天时，ＴＧ细胞内出现ＨＳＶ－１抗原阳性，第１０天时培养细胞开始呈现细胞病变，第２～３周内全部潜伏感染的ＴＧ培养细胞出现自发性感染，ＣＰＥ和ＨＳＶ－１抗原原均为阳性，在体外成功地建立了潜伏感染ＴＧ活化的细胞模型，为进一步研究ＨＳＶ－１在Ｇ胞内的潜伏感染机制提     

大鼠角膜热烧伤后眼组织平片的免疫组织化学研究

目的:探讨角膜热烧伤后角膜溃烂溶解穿孔以及眼内炎症的免疫学机制。方法:在大鼠角膜上制作热烧伤模型,在烧伤后的不同阶段,制备角膜,虹膜、脉络膜巩膜复合体以及视网膜平片,采用标准的ABC免疫组化方法,观察眼局部T淋巴细胞亚群,巨噬细胞、树突细胞,MHC Ⅱ类抗原阳性细胞的动态变化。结果:烧伤后早期,角膜及虹膜即有T淋巴细胞浸润,以CD3阳性细胞为主,MHCⅡ类抗原阳性细胞也轻度增多;当角膜溶解穿孔阶段,T淋巴细胞浸润达到高峰,在T淋巴细胞亚群中,CD4明显多于CD8阳性细胞;同时,巨噬细胞、树突细胞、MHCⅡ类抗原阳性细胞也大量出现。细胞密集分布于角膜缘,在溃疡溶解处,可见MHCⅡ类抗原阳性细胞及少至中等量CD3阳性淋巴细胞。Ⅱ类抗原阳性细胞在形态学上也发生了些变化,由初期的园形变为多形性,且大小不一。当烧伤恢复期病变稳定时,各种阳性细胞逐渐减少。结论:免疫反应参与了严重角膜烧伤的发病过程,在角膜溶解穿孔的发生中起重要作用。眼科学报 1997;13:70～74。     

T lymphocytes in the trigeminal ganglia of rabbits during corneal HSV infection

The results of this investigation reveal, for the first time, the presence of thymus-derived (T) lymphocytes in the trigeminal ganglia of rabbits undergoing primary corneal infection with herpes simplex virus type 1. Infiltration of T cells into the trigeminal ganglion was evident at 15 days after primary ocular infection but these cells were no longer present by 45 days after infection. Corneas and trigeminal ganglia of rabbits sacrificed at 3, 7, 12, 15, 20, 25, 30, 45, 70 and 90 days after infection were assayed for infectious virus and stained for viral antigen and immunoreactive T cells. Infectious virus and cells expressing viral antigens were present in the corneas and trigeminal ganglia during the acute phase (day 0-day 14) of the infection. T cell infiltration of the trigeminal ganglion was present as a perivascular infiltrate along with a sparse scattering of these cells among the nerve fibers. The perivascular infiltration is characteristic of viral infection of a tissue and was not seen in the sections of trigeminal ganglia obtained earlier than 15 days or in ganglia obtained 45 days or more after primary corneal infection. This investigation demonstrates conclusively that the neural ganglia are not completely shielded from the host immune response, as evidenced by the observation that immunocompetent T lymphocytes infiltrate the ganglia subsequent to the infection of a peripheral tissue such as the cornea of the eye.     

The isolation of herpes simplex virus from rabbit corneas during latency

Herpes simplex virus type 1 (HSV-1) latency, as operationally defined, is a state in which cell-free infectious virus cannot be demonstrated in tissue at the time of sacrifice, but infectious virus can be isolated from the same tissue after prolonged cultivation. Latent HSV has been routinely detected in sensory ganglia of the infected dermatome. We have isolated HSV-1 (RE) from the corneas of 11% of infected rabbits which harbored virus in a latent state in trigeminal ganglia. HSV-1 (RE) was isolated from 10 of 88 cultures of corneal cells established following collagenase digestion of individual corneas taken from asymptomatic animals 118 days after infection. Virus was recovered only after prolonged primary culture and in some cases serial passage of corneal cells (range 5 to 26 days to initial cytopathic effect, n = 10). Virus was isolated from 68 of 68 trigeminal ganglia from the same rabbits by cocultivation of ganglion pieces with Vero cells (range 9 to 20 days to initial cytopathic effect, n = 68) while no cell-free virus was isolated from ganglia at the time of sacrifice. Virus isolation from corneas during the latent period occurred in a manner independent of prior antiviral or antiviral plus immunosuppressive therapy. Clinical evaluation of the corneas throughout the course of acute disease, stromal disease, and at the time of sacrifice provided no evidence that could be used to predict which corneas would yield virus. These data suggest that HSV-1 can remain in a nonreplicative state characteristic of latency in cells of rabbit corneas for long periods after infection and therapy of herpetic eye disease.     

实验性单纯疱疹病毒Ⅰ型感染兔眼部扫描电镜观察研究

应用ＤＭＳＯ（Ｄｉｍｅｔｈｙｌｓｕｌｆｏｘｉｄｅ二甲基亚砜）冷冻割断制样扫描电镜技术首次动态观察了不同感染阶段（ｐｏｓｔＩｎｆｅｃｔｉｏｎ，ＰＩ）实验性单纯疱疹病毒性角膜炎（ＨＳＫ）兔的角膜、三叉神经节（ＴＧ）泪腺等组织的病变情况。初步报告并分析了各组织病变的扫描图像结果，并对冷冻割断法观察扫描电镜的原理及优缺点予以讨论，认为该技术应用于眼部单疱病毒感染的研究图像清晰、直观、简便可行，是一种有实用价值的方法。     

Peripheral adrenergic stimulation and indomethacin in experimental ocular shedding of HSV

The application of 6-hydroxydopamine to the cornea by iontophoresis, followed by topical epinephrine, effectively induces herpes simplex virus (HSV) shedding from the external eye of latently infected rabbits. In this study the beta adrenergic blocker, Timolol, reduced virus shedding when applied immediately before the epinephrine, but continued administration resulted in increased viral shedding. While indomethacin, a prostaglandin synthesis inhibitor decreased HSV replication in cell culture, it failed to decrease virus shedding when applied topically to the eye in adrenergically stimulated animals. Timolol may act then by its effect on the peripheral cells of the eye rather than by stimulation of virus production in ganglionic neurons. These same animals were subsequently tested for latent infection of the trigeminal and superior cervical ganglia and corneas 14 months after primary infection. Only 2 of 14 animals had virus in the trigeminal ganglia, a finding which suggests that latent virus may be depleted by repeated reactivations. Virus was recovered from corneas of five rabbits by co-cultivation so it is possible that corneal latency occurs in this rabbit model as it does in humans.     

Herpesvirus infection of ICAM-1-deficient mice

PURPOSE: To determine the effect of ICAM-1 deficiency on viral infection of the cornea. MATERIALS AND METHODS: Wild-type and intercellular adhesion molecule 1 (ICAM-1)-deficient mice were infected with the RE strain of herpes simplex virus type 1 (HSV-1). Corneal swabs and trigeminal ganglia were obtained and analyzed for infectious virus. Corneas and trigeminal ganglia were evaluated for signs of inflammation by immunohistochemical staining and for interferon-gamma (IFN-gamma)-producing cells by enzyme-linked immunospot assay (ELISPOT). Serum anti-HSV-1 antibody titers were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Viral titers in corneal swabs from the wild-type and ICAM-1-deficient mice were not significantly different during the 21-day study. Infectious virus was present in the trigeminal ganglia of wild-type and ICAM-1-deficient mice through day 6 after infection. Serum anti-HSV-1 antibody titers were significantly higher in wild-type mice 6 days after infection, compared with ICAM-1-deficient mice; by day 8 and thereafter, however, antibody titers were not significantly different. Production of interferon gamma was greater in trigeminal ganglion cells from wild-type mice stimulated with interleukin 12 and interleukin 18 on days 4, 6, and 8 after infection compared with cells from ICAM-1-deficient mice. Histopathologic analysis of corneal and ganglion sections from wild-type and ICAM-1-deficient mice showed no significant differences in the time-course of appearance or the intensity of the inflammatory infiltrate. Immunohistochemical staining for CD3(+) T-lymphocytes and CD11b(+) neutrophils and macrophages demonstrated equivalent numbers of these cells in the corneas and trigeminal ganglia of wild-type and ICAM-1-deficient mice. CONCLUSIONS: The results of these experiments indicate that ICAM-1 deficiency has only a modest effect on viral infection of the cornea and the development of an acquired immune response.     

Changes in gene expression in latent HSV-1-infected rabbit trigeminal ganglia following epinephrine iontophoresis

PURPOSE: The aim of the present study was to identify the genes that express in the nervous system when herpes simplex virus type 1 (HSV-1) reactivates from latency by using subtraction cloning following epinephrine iontophoresis. METHODS: The corneas of New Zealand White rabbits (2 to 2.5 kg) were topically inoculated with 5 x 10(5) PFU of plaque-purified HSV-1 strain McKrae. Corneal infection was monitored by slit lamp examination (SLE) on days 3-7 after infection. At 30 d post-infection, eyes were assessed for infectious virus by ocular swabs. Disappearance of virus in ocular swabs signified latency for HSV-1. Latently-infected rabbits were subjected to transcorneal iontophoresis. The messenger RNA (mRNA) was isolated from the trigeminal ganglia and used for subtraction cloning and subtraction library synthesis. RESULTS: Our results indicate 18 genes with increased expression and 6 genes with decreased levels. Northern blot analysis revealed that genes for OX-40 ligand, MHC class II HLA-DR-alpha and beta-microglobulin showed predominant increase followed by tyrosine 3'-monooxygenase, proteolipid protein, tyrosine beta, and apolipoprotein D. Genes that underwent reduced expression included cytochrome c oxidase subunit I, ATP synthase isoform, cytochrome b, ATPase 9, and at least one unidentified gene. CONCLUSIONS: Our results, particularly the increased detection of OX-40 ligand and MHC class II-alpha and beta-2 microglobulin, support the finding that lymphocytes persist in latently-infected trigeminal ganglia (TGs). These results also suggest a role of the immune system in HSV-1 recurrences. In addition, we have detected genes associated with neuronal disorders, OX-40L, proteolipid protein, and apolipoprotein D.     

Experimental reactivation of ocular herpes simplex in rabbits

Latent herpes simplex virus (HSV) is known to reside in the trigeminal ganglia. Our studies show that the temporay retrobulbar disruption of trigeminal nerve function in chronically infected animals caused a striking decrease in the number of positive HSV cultures obtained during the 20 weeks immediately following surgery. We found that the stereotaxic interruption of intracranial trigeminal nerve function prior to initial HSV infection dramatically reduced the incidence of peripheral recurrence of HSV. Stereotaxic stimulation of the trigeminal ganglion in chronically infected animals produced a significant increase in positive cultures within two days. But, direct neurosurgical stimulation of the trigeminal ganglion proved strikingly effective, producing 83% positive cultures at the eye within 48 hours of operation. These studies further substantiate the premise that the trigeminal ganglion serves as a reservoir for latent ocular HSV in rabbits. They also suggest that the transmission of latent HSV from the trigeminal ganglion to its infectious form in the peripheral ocular tissues somehow involves the trigeminal nerve.     

The effect of trigeminal nerve and ganglion manipulation on recurrence of ocular herpes simplex in rabbits.

Latent herpes simplex virus (HSV) has been demonstrated in the trigeminal ganglia of experimentally infected rabbits between episodes of spontaneous ocular recurrence. In three experiments reported here, the normal pattern of recurrence was modified by manipulation of the trigeminal nerve and ganglion. Temporary retrobulbar disruption of trigeminal nerve function in chronically infected animals significantly decreased the number of ocular HSV isolations obtained during the 20 weeks immediately following surgery. Stereotaxic interruption of intracranial trigeminal nerve function prior to initial HSV infection dramatically reduced the incidence of peripheral recurrence of HSV. In chronically infected animals, stereotaxic stimulation of the trigeminal ganglion caused a marked increase in positive cultures within 2 days. These studies provide additional evidence for the theory that the reservoir for latent ocular HSV in rabbits is the trigeminal ganglion. Moreover, the studies suggest that the transmission of latent HSV from the trigeminal ganglion to its infectious form in the peripheral tissues involves the trigeminal nerve. We have shown that mechanical and stereotaxic stimulation of the trigeminal ganglion is a reliable and rapid means of precipitating peripheral ocular shedding of HSV on command, a finding which should prove most productive in future research.     

Suppression of secondary herpes simplex uveitis by cyclosporine

The authors studied the effect of an immunosuppressive agent, cyclosporine (CyA), on experimental secondary herpes simplex (HS) uveitis. Secondary HS uveitis was induced in a rabbit eye that had recovered from primary HS uveitis by challenging it with an intravitreal injection of herpes simplex virus (HSV) antigen. Daily intramuscular injections of CyA (25 mg/kg body weight) for 7 days prior to the intravitreal challenge with HSV antigen significantly suppressed the induction of secondary HS uveitis, but daily injections of CyA after the challenge with HSV antigen was ineffective. Intravitreal injections of CyA (5 mg) 7 days and 3 days prior to the HSV challenge were less effective, but the combined treatment with seven daily intramuscular CyA and two intravitreal CyA injections prior to the HSV challenge was most effective in the prevention of the uveitis. The daily intramuscular treatment with CyA resulted in a marked reduction of cell-mediated immunity while leaving the level of circulating HSV specific antibody high. No reactivation of latent HSV was detected in trigeminal and superior cervical ganglia of CyA-treated rabbits.     

Role of lymphocyte and antibody in the pathogenesis of immune-mediated herpetic uveitis

We investigated the role of various immune components in the pathogenesis of immune-mediated experimental herpetic uveitis. Inbred III/J strain of rabbits were sensitized with an intravitreal injection of 10(3) PFU of type 1 herpes simplex virus (HSV), and sensitized cervical lymph node (LN) cells were obtained on postinfection day 12. Intravitreal injection to the normal III/J rabbit eye of HSV antigen with either sensitized LN cells or anti-HSV serum failed to induce uveitis, whereas intravitreal injection of HSV-antigen with both sensitized LN cells and anti-HSV serum produced severe uveitis within six hours. The combination of sensitized LN cells, HSV-antigen and normal rabbit serum, or that of normal LN cells, HSV antigen and anti-HSV serum, did not induce uveitis. Further studies using B lymphocyte and T lymphocyte fractions from sensitized LN showed that only the combination of sensitized T lymphocytes, HSV antigen and anti-HSV serum regularly produced uveitis following intravitreal injection. These results indicate that the interaction of HSV antigen, sensitized T lymphocytes and anti-HSV antibody may play a role in the pathogenesis of immune-mediated herpetic uveitis.