The retina represents a highly specialized structure with the primary function to capture a light signal and to convert it into electrical impulses. Any damage or disease of the retina can cause visual impairment. Since retinal degenerative diseases are generally associated with immune cell infiltration, a local inflammatory reaction, and cytokine burn, there is a need for mechanisms to prevent the retina from damage by a deleterious immune reaction. In this study, we show that mouse retinal explants co-cultivated with stimulated spleen cells, inhibit in a dose-dependent manner the activation of T cells, and suppress the production of cytokines interleukin-2, interleukin-10, and interferon-[Formula: see text]. The immunoregulatory properties of the retina were mainly mediated by a paracrine effect since retinal explants, separated by a semipermeable membrane, or supernatants obtained after the cultivation of retinal explants, inhibited the reactivity of immune cells. A model of retinal damage was established by the application of sodium iodate which selectively destroys photoreceptors, as it was demonstrated by a decrease in the number of rhodopsin-positive cells. This process was accompanied by increased infiltration of the retina with cells of the immune system and by a local inflammatory reaction. The pharmacologically damaged retina had significantly decreased the ability to inhibit T cell activation and production of cytokines by immune cells. Overall, the results showed that the retina possesses immunoregulatory properties and inhibits the activation and functions of T cells. However, the immunomodulatory properties of the retina are decreased if the retina is damaged.

• Keywords
• cytokines, healthy retina, immunosuppression, inflammatory eye, pharmacologically damaged retina,
• MeSH
• Cytokines * metabolism   MeSH
• Mice MeSH
• Retina * MeSH
• Inflammation metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cytokines * MeSH

The eye has been described as an immunologically privileged site where immunity is purely expressed. It has been demonstrated that administration of antigen into the eye induces only a weak immune response. However, the anterior part of the eye represents an important protective barrier against pathogens and other harmful invaders from the outer environment. Therefore, effective immune mechanisms, which operate locally, need to be present there. Because the cornea has been shown to be a potent producer of various cytokines and other molecules with immunomodulatory properties, we investigated a possible regulatory role for the individual corneal cell types on cytokine production by activated T cells. Mouse spleen cells were stimulated with the T cell mitogen concanavalin A in the presence of either corneal explants or cells of corneal epithelial or endothelial cell lines and the production of T helper 1 (Th1) or Th2 cytokines was determined by enzyme-linked immunosorbent assay (ELISA) or reverse transcription-polymerase chain reaction (RT-PCR). We found that the cornea possesses the ability to inhibit, in a dose-dependent manner, production of the inhibitory and anti-inflammatory cytokines interleukin (IL)-4 and IL-10 by activated T cells. The production of cytokines associated with protective immunity [IL-2, IL-1beta, interferon (IFN)-gamma ] was not inhibited under the same conditions. Corneal explants deprived of epithelial and endothelial cells retained the ability to suppress production of anti-inflammatory cytokines. This suppression was mediated by a factor produced by corneal stromal cells and occurred at the level of cytokine gene expression. We suggest that by this mechanism the cornea can potentiate a local expression of protective immune reactions in the anterior segment of the eye.

• MeSH
• Lymphocyte Activation MeSH
• Cytokines biosynthesis   MeSH
• Enzyme-Linked Immunosorbent Assay methods   MeSH
• Interferon-gamma analysis   genetics   MeSH
• Interleukin-1 biosynthesis   MeSH
• Interleukin-10 biosynthesis   MeSH
• Interleukin-2 biosynthesis   MeSH
• Interleukin-4 biosynthesis   genetics   MeSH
• Coculture Techniques MeSH
• Concanavalin A pharmacology   MeSH
• Culture Techniques MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Spleen MeSH
• Corneal Stroma immunology   MeSH
• T-Lymphocytes immunology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cytokines MeSH
• Interferon-gamma MeSH
• Interleukin-1 MeSH
• Interleukin-10 MeSH
• Interleukin-2 MeSH
• Interleukin-4 MeSH
• Concanavalin A MeSH

Oral administration of antigen has been shown to be effective for both positive and negative modulation of immune responses. In the present study we characterized changes in the reactivity of the immune system after oral immunization with allogeneic spleen cells. Mice were orally immunized for 10 consecutive days with fresh allogeneic spleen cells, and the phenotype, proliferative response, cytotoxic activity and cytokine production profile of recipient spleen cells were assessed 1 or 7 days after the last immunization dose. Although no significant changes in the proportion of CD4+, CD8+ or CD25+ cells were observed in the spleen of orally immunized mice, significant activation of alloreactivity in spleen cells was found. Cells from orally immunized mice exhibited enhanced proliferation and cytotoxic activity after stimulation with specific allogeneic cells in vitro, and produced considerably higher concentrations of interferon-gamma (IFN-gamma) and significantly less interleukin (IL)-4 than did cells from control mice. The production of IL-2 was essentially unchanged and that of IL-10 was only slightly increased. The systemic allosensitization induced by oral immunization was demonstrated in vivo by increased resistance to the growth of allogeneic tumours induced by subcutaneous inoculation of high doses of tumour cells. In addition, orthotopic corneal allografts in orally immunized recipients were rejected more rapidly (in a second-set manner) than in control, untreated recipients. These data show that oral immunization with allogeneic cells modulates individual components of the immune response and that specific transplantation immunity, rather than tolerance, is induced in the treated recipients.

• MeSH
• Administration, Oral MeSH
• Cell Division immunology   MeSH
• Cholera Toxin immunology   MeSH
• Cytokines biosynthesis   MeSH
• Cytotoxicity, Immunologic MeSH
• Sarcoma, Experimental prevention & control   MeSH
• Immunization methods   MeSH
• Immunophenotyping MeSH
• Mice, Inbred Strains MeSH
• Humans MeSH
• Mice MeSH
• Graft Survival immunology   MeSH
• Spleen immunology   transplantation   MeSH
• Lymphocyte Culture Test, Mixed MeSH
• Neoplasm Transplantation MeSH
• Corneal Transplantation immunology   MeSH
• Transplantation Immunology * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cholera Toxin MeSH
• Cytokines MeSH

BACKGROUND: Urocanic acid (UCA) is a natural component of the stratum corneum of the skin. It has been described as a photoreceptor for ultraviolet B radiation. UCA is present in the skin as a trans-isomer and undergoes UVB irradiation-dependent isomerization from trans-to cis-isomer. An immunosuppressive effect of irradiated UCA, i.e. a mixture of cis- and trans-isomers, has been demonstrated both in vivo and in vitro. The aim of this study was to evaluate an immunosuppressive effect of irradiated UCA on graft rejection in an experimental model of orthotopic corneal transplantation. METHOD: A commercially available UCA was dissolved in salt solution and irradiated by XeCl excimer laser beam in order to obtain a mixture of cis- and trans-isomers. The immunosuppressive effect of irradiated UCA, compared to controls, unirradiated UCA and salt solution, was evaluated in a high-risk orthotopic corneal transplantation model; the agents were administered subconjunctivally to rabbits. RESULTS: The rejection reaction was observed in all animals. The mean graft survival time in rabbits administered salt solution or unirradiated UCA was 20 days and 22 days, respectively. The irradiated solution of UCA significantly (P < 0.01, Mantel-Cox test) prolonged mean graft survival time to 29 days. CONCLUSION: Subconjunctival administration of irradiated UCA prolonged the graft survival time in comparison with unirradiated UCA or salt solution in recipients in a rabbit transplantation model. Although further studies are necessary, UCA seems to be an effective immunosuppressive drug after corneal transplantation.

• MeSH
• Chinchilla MeSH
• Immunosuppression Therapy methods   MeSH
• Injections MeSH
• Conjunctiva MeSH
• Rabbits MeSH
• Urocanic Acid pharmacology   radiation effects   MeSH
• Lasers MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Graft Survival drug effects   MeSH
• Graft Rejection drug therapy   pathology   MeSH
• Cornea drug effects   pathology   MeSH
• Transplantation, Heterologous MeSH
• Corneal Transplantation * MeSH
• Treatment Outcome MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• Urocanic Acid MeSH