[The immunoregulatory role of local antigen-presenting cells in ocular inflammation].
The immune privilege that exists in the eye is maintained by various mechanisms. One of the best studied is a form of systemic tolerance termed anterior chamber-associated immune deviation (ACAID). We have recently shoun that the vitreous cavity(VC) also had the ability to induce tolerance and named this phenomenon 'vitreous cavity-associated immune deviation(VCAID). Ocular antigen-presenting cells(APCs) are known to be critical in inducing both ACAID and VCAID. In contrast to normal conditions, an inflamed eye no longer supports either ACAID or VCAID induction. We therefore elucidated the mechanism for terminating already established ocular inflammation. Murine experimental autoimmune uveitis (EAU) is a model of human uveitis. Ocular-infiltrating macrophages produce various cytokines/chemokines and damage tissue in EAU. We found that only the macrophage-enriched cells from the eye produced RANTES(regulated upon activation normal T cells expressed and secreted) Neutralization of RANTES by specific antibodies in vivo exacerbated EAU. We also found that the ratio of ocular CD 4/CD 8 T cells was markedly increased after treatment. As a result, RANTES neutralization might exacerbate EAU by modulating the type of T cell subsets recruited to the eye. Our data provide insight into the immunoregulatory role of macrophages mediated by RANTES in the pathogenesis of ocular inflammation. Not all macrophage-derived chemokines may cause local inflammation, since RANTES produced by ocular macrophages appears to suppress experimental autoimmune uveitis.
Sonoda
Koh-Hei
KH
Department of Ophthalmology, Graduate School of Medical Science, Kyushu University. 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. sonodak@med.kyushu-u.ac.jp
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D018946:Chemokine CCL5 / Q000032:analysis / Q000276:immunology*; D004195:Disease Models, Animal; D007108:Immune Tolerance; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D014605:Uveitis / Q000276:immunology*
D018946:Chemokine CCL5