Published online before print June 22, 2006
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* Laboratories of Immunology and
Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland;
Laboratory of Molecular Immunoregulation, National Cancer Institute, National Institutes of Health, Frederick, Maryland; and
Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School, Japan
1 Correspondence: Laboratory of Immunology, National Eye Institute, NIH, Building 10, Room 10N208, 10 Center Drive, Bethesda, MD 20892-1857. E-mail: geryi{at}nei.nih.gov
ABSTRACT
Immune cell-mediated inflammatory responses are triggered by TCR engagement with the target antigen, the initial event that brings about the complex sequence of events of the inflammatory process. Another form of inflammation is induced by local expression of certain cytokines. Unlike the former form of inflammation, little is known about the basic features of the cytokine-induced responses. Here, we analyzed tissue morphology, the infiltrating cells, and up-regulated, inflammation-related genes in mouse eyes in which inflammation is triggered by local transgenic (Tg) expression of cytokines and compared these features with those in eyes with experimental autoimmune uveitis (EAU), in which inflammation is initiated by engagement of TCR on sensitized T cells with their target antigen, followed by the well-defined, subsequent cytokine production. Eyes of IFN-
Tg mice exhibited severe, morphological changes but essentially no inflammation, and intense inflammation was found in eyes of interleukin (IL)-1 or IL-7 Tg mice. The cellular infiltration in eyes of these latter two lines of Tg mice resembled that in eyes with EAU by including many CD4 cells, but unlike in EAU, the infiltration in Tg eyes contained large proportions of B cells and only small numbers of macrophages. Real-time PCR analysis of eye RNA revealed differences among the disease models in the expression profiles of various inflammation-related genes. It is interesting that a bias toward T helper cell type 1 immunity (high IFN-, RANTES/CCL5, MIG/CXCL9, and T-bet but low IL-4, IL-5, and GATA-3 transcripts) was found in EAU eyes but not in eyes of IL-1 and IL-7 Tg mice. The results thus show that similar to TCR engagement, local expression of certain cytokines triggers a complex, subsequent production of numerous inflammation-related molecules, but features of the ensued inflammatory process are determined by the triggering mechanism.
Key Words: immune-mediated inflammation • eye • experimental autoimmune uveitis (EAU) • transgenic mice
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