Orchestrated leukocyte recruitment to immune-privileged sites: absolute barriers versus educational gates.

Complex barriers separate immune-privileged tissues from the circulation. Here, we propose that cell entry to immune-privileged sites through barriers composed of tight junction-interconnected endothelium is associated with destructive inflammation, whereas border structures comprised of fenestrated vasculature enveloped by tightly regulated epithelium serve as active and selective immune-skewing gates in the steady state. Based on emerging knowledge of the central nervous system and information from other immune-privileged sites, we propose that these sites are endowed either with absolute endothelial-based barriers and epithelial gates that enable selective and educative transfer of trafficking leukocytes or with selective epithelial gates only.

Total protein concentration and T-cell suppression activity of aqueous humour before and after penetrating keratoplasty.

PURPOSE: We wished to determine whether immune privilege parameters assayed in aqueous humour (AqH) are relevant to the fate of penetrating keratoplasty (PK) in humans. METHODS: AqH was collected in 28 patients before PK (prospective cohort), in 6 patients with no history of graft rejection undergoing cataract surgery after PK (acceptors), in another 6 patients undergoing treatment of an acute endothelial immune reaction (rejectors), and in 65 controls undergoing uncomplicated cataract extraction. AqH was tested for total protein concentration and the ability to suppress T-cell activation. RESULTS: AqH protein concentrations of acceptors and rejectors post-PK were elevated (2.7 ± 0.8 and 2.7 ± 0.7 mg/ml, respectively) compared with pre-PK AqH level and cataract controls (1.0 ± 0.1 mg/ml, P = 0.01). All AqH samples suppressed T-cell activation, irrespective of source and timing of AqH removal. CONCLUSION: Assays of immune privilege markers in AqH suggest that PK surgery may result in a sustained loss of integrity of the blood-aqueous barrier. Although trends were evident, values of immune privilege markers determined pre- and post-PK were not statistically significantly different between the study groups. However, further prospective studies determining additional immune privilege markers have to be conducted in order to find out whether these markers might serve as predictive parameters for immune reactions following PK.

Clinical scoring and biophysical evaluation of nasolabial skin barrier damage caused by rhinorrhea.

BACKGROUND: An acute viral cold is a very common illness and is characterized by sneezing and a runny nose. Because of rhinorrhea and frequent use of handkerchiefs, the skin around the nose feels uncomfortably dry and flaky. OBJECTIVES/METHODS: To evaluate the nasolabial skin barrier impairment, 14 female volunteers with a common cold were recruited. Visually assessed clinical scoring and/or biophysical measurements--including transepidermal water loss, stratum corneum hydration, skin colour, squamometry, skin pH, and a skin surface lipid profile analysis--were carried out at the start of the cold, a second time when the severity of the cold symptoms was maximal, and finally when the volunteers felt healthy again and stopped using handkerchiefs. RESULTS AND CONCLUSIONS: Transepidermal water loss assessments showed significantly higher measurements on the maximum outcome of the nasal cold compared with the time-point when the symptoms of the cold had disappeared. This was in accordance with skin colour chroma a* measurements and the visually assessed skin erythema and scaliness scores, indicating that the superficial nasolabial skin barrier was inferior at the maximum of a nasal cold in comparison with the skin condition when volunteers were fully recovered.

[The immune system and the eye]. / Immunsystemet og øjet.

The special relationship between the eye and the immune system rests on a number of anatomical, physiological and immunological mechanisms. These mechanisms prevent the delicate structures of the eye from potentially damaging immunogenic inflammation while protecting against pathogens. Rather than inflammation, antigen induces a form of systemic and antigen-specific immunological tolerance. Owing to its systemic nature, this tolerance may be utilised to achieve successful treatment of immunological disorders.

[Ocular toxoplasmosis antibodies in aqueous humor and serum]. / Okuläre Toxoplasmose-Antikörper in Kammerwasser und Serum.

BACKGROUND: The diagnosis of ocular toxoplasmosis is mainly based on ophthalmological examination but might be difficult to establish in some cases. The purpose of our study was to evaluate the value of aqueous humor and serum analysis in ocular toxoplasmosis. PATIENTS AND METHODS: We analyzed the avidity of toxoplasma-specific IgG in aqueous humor and serum samples from 50 patients with toxoplasmic retinochoroiditis, with 25 patients with uveitis posterior or panuveitis serving as controls. RESULTS: Specific intraocular antibody synthesis could be confirmed in 49 patients (98%). In two patients (8%) of the control group, antibody synthesis was detected (false positive). Forty-nine patients with diagnoses of ocular toxoplasmosis were positive for serum anti-T. gondii IgG, but only three patients had increased IgM levels. CONCLUSIONS: Analysis of local antibody production is a reliable method for confirming or excluding a suspected clinical diagnosis of toxoplasma retinochoroiditis. The determination of toxoplasma antibodies in the patients' serum is of limited value.

IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis.

PURPOSE: To determine the immunosuppressive status of aqueous humor (AqH) from mouse eyes afflicted with endotoxin-induced uveitis (EIU) and to identify the relevant cytokines responsible for immunomodulatory activity within EIU AqH. METHODS: Bacterial lipopolysaccharide (LPS) was injected into hind footpads of C3H/HeN mice; and AqH, collected at 6, 12, 24, and 48 hours, was evaluated for content of transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and interferon (IFN)-gamma and capacity to suppress anti-CD3-driven T-cell proliferation. Cytokine mRNA expression in iris-ciliary body (I/CB) was analyzed by RNase protection assays. RESULTS: During 6 to 24 hours after LPS injection, total TGF-beta levels in AqH increased even though the fluid lost its capacity to suppress T-cell activation. At this time, AqH contained high levels of IL-6, and I/CB contained high levels of IL-6 mRNA. When IL-6 was neutralized with specific antibodies, inflamed AqH reacquired its capacity to suppress T-cell activation, which correlated with high levels of TGF-beta. Coinjection of IL-6 plus antigen into the anterior chamber of the eye of normal mice prevented antigen-specific anterior chamber-associated immune deviation (ACAID). CONCLUSIONS: LPS-induced intraocular inflammation is associated with local production of IL-6, which robs AqH of its immunosuppressive activity, perhaps by antagonizing TGF-beta. The fact that IL-6 antagonized ACAID induction in normal eyes suggests that strategies to suppress the intraocular synthesis of IL-6 may reduce inflammation and restore ocular immune privilege.

Effects of experimental ocular inflammation on ocular immune privilege.

PURPOSE: To determine whether the inflammation of endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU) alters key in vivo and in vitro parameters of ocular immune privilege. METHODS: For EIU induction, C3H/HeN mice received 200 microg lipopolysaccharide (LPS). For EAU induction, B10.A mice were immunized with 50 microg interphotoreceptor retinoid-binding protein (IRBP) mixed with complete Freund's adjuvant. Aqueous humor (AqH) was collected at periodic intervals and assayed for leukocyte content and the ability to suppress or enhance T-cell proliferation. Eyes with EAU were assessed for the capacity to support anterior chamber (AC)-associated immune deviation (ACAID) induction after injection of ovalbumin (OVA). RESULTS: Inflammation within the anterior segment in EIU peaked at 12 to 24 hours and was detected from 10 days onward in EAU. In AqH of EIU, protein content rose within 4 hours, followed by infiltrating leukocytes. EIU AqH promptly lost its capacity to suppress T-cell proliferation and became mitogenic for T cells. In AqH of EAU, protein and leukocyte content rose at 11 days and continued to remain elevated thereafter. Whereas 11-day EAU AqH failed to suppress T-cell proliferation, AqH at later time points reacquired immunosuppressive properties. Injection of OVA into the AC of eyes of mice with EAU failed to induce ACAID. CONCLUSIONS: The intraocular inflammation of EIU and EAU disrupted important parameters of immune privilege, ranging from breakdown of the blood- ocular barrier, to loss of an immunosuppressive microenvironment, to abrogation of ACAID. Because AqH from inflamed EAU reacquired the ability to suppress T-cell proliferation, the authors conclude that the capacity to regulate immune expression and inflammation can be a property even of inflamed eyes.

CD4+ T cell/CD8+ T cell ratio in the anterior chamber of the eye after penetrating injury and its comparison with normal aqueous samples.

We have recently reported that significantly more CD8+ T-cell activity is present in the aqueous humor compared to peripheral blood. The aim of the current study is to investigate the effect of the ocular trauma on the number of the T lymphocyte subsets in the aqueous humor. CD4+/CD8+ T-cell ratios in the aqueous and blood samples of 12 patients who suffered from traumatic iridocyclitis because of a corneal perforation were compared to those of patients with senile cataracts. We found a relatively higher CD4+/CD8+ cell ratio in the aqueous samples of traumatized patients than cataractous patients. Meanwhile, no difference was present between the aqueous and blood samples of the traumatized patients with respect to the above-mentioned ratio. We suggest that one of the most important factors in maintaining a lower CD4+/CD8+ cell ratio in normal aqueous humor compared to peripheral blood is an intact blood-aqueous barrier. Blood-aqueous barrier may play a participating role in the pathogenesis of immunosuppressive properties of the anterior chamber of the eye by establishing higher CD8+ T-cell activity in the aqueous humor relative to the peripheral blood.

[Immune reactions in the eye]. / Les réactions immunitaires dans l'oeil.

The immunological status of the eye, like the one of the brain, is generally considered as an "immune privilege" site because of the presence of a strong blood-ocular barrier, the lack of lymphatic drainage and, last but not the least, the absence of professional antigen-presenting cells. This dogma is now challenged by recent studies indicating that presentation of endogenous (as in autoimmune uveitis) or exogenous (like in ocular cysticercosis) antigens occurs. The local immune response seems regulated by active immunosuppressive mechanisms, in order to limit the destructive effect of inflammatory reactions.