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Abstract #15355 Published in IGR 1-3
Specific aqueous humor factors induce activation of regulatory T cells
Nishida T; Taylor AWInvestigative Ophthalmology and Visual Science 1999; 40: 2268-2274
PURPOSE: To examine the possibility that aqueous humor-induced regulatory T cells could function in vivo, these T cells were examined for their ability to suppress adoptive transfer of delayed-type hypersensitivity (DTH). To begin to understand the mechanisms by which aqueous humor induces activation of regulatory T cells, α-melanocyte stimulating hormone (MSH) and transforming growth factor (TGF)-β2 were examined for ability to induce regulatory T cells. METHODS: Primed T cells were treated with aqueous humor and assayed for regulatory activity by injecting them intravenously along with DTH-mediating T cells into syngeneic mice. Antigen-pulsed antigen-presenting cells (APCs) were injected into the pinna of the mouse ear, and swelling was measured 24 hours later. Primed T cells were also activated in vitro in the presence of α-MSH, TGF-β1, or TGF-β2 and were assayed for proliferation and TGF-β production along with suppressing DTH. RESULTS: Aqueous humor-treated T cells suppressed inflammation mediated by DTH T cells. Maximum regulatory T cell activity was induced when primed T cells were activated in vitro in the presence of α-MSH followed four hours later with active TGF-β2. Such T cells proliferated, produced TGF-β, and suppressed DTH, suggesting that α-MSH and TGF-β2 induce activation of regulatory T cells. No regulatory T cell activity could be induced in the presence of TGF-β1. CONCLUSIONS: The ocular microenvironment constitutively produces immunoregulatory factors that suppress the induction of inflammatory activity and promotes regulatory T-cell activity. Such regulatory T cells can further contribute to maintaining the normal immunosuppressive ocular microenvironment through their ability to suppress activation of other inflammatory T cells.
Dr. T. Nishida, Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, Boston, MA 02114; USA
Classification:
2.6 Aqueous humor dynamics (Part of: 2 Anatomical structures in glaucoma)
