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R. Pais, S. Chattopadhyay, Y. Lemire, R. Sharafieh, S. Bhowmick, J. O'Rourke, R. E. Cone; ACAID Is Initiated as a Result of a Moderate Inflammatory Insult to the Anterior Chamber. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4835.
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Objective: Anterior chamber-mediated Immune deviation (ACAID) is induced by the injection of antigen (Ag) into the anterior chamber (AC) and is transmitted by iris-derived F4/80+monocytes that home to the thymus and spleen where they initiate events that culminate in the development of splenic CD8+ suppressor T cells. We have shown previously that F4/80+ PBMC infiltrate the Iris in response to intracameral injection with or without antigen. Expression of the chemokine receptor CCR2 is required for PBMC infiltration after the intracameral injection of Ag and the subsequent generation of circulating F4/80+ cells that induce ACAID. These observations suggest that the induction of ACAID may be a result of moderate injury that induces inflammatory mediators that attract circulating F4/80+ monocytic cells to the anterior chamber.
Aqueous humor (AH) was collected by paracentesis and assayed by ELISA for MCP-1, MCP-3 and TNF-α. Neutralizing antibodies to MCP-1, TNF-α, TGF- β and PDTC, an inhibitor of NFΚB activation were injected into the AC to study their impact on AC chemokine, TNF-α levels and monocyte infiltration into the iris post AC injection.
indicate that there is a time-dependent increase in the chemokines MCP-1 and MCP-3 and the inflammatory cytokine TNF -α in AH following intracameral injection. Blockade of TNF-α with anti-TNF-α caused a decrease in MCP-1 in AH. Injection of either anti-TGF-β or the TGF-β receptor kinase inhibitor (SB-431542) (a) did not affect the MCP-1 levels in AH, (b) caused some reduction of TNF-α, (c) minimized the infiltration of circulating PBMCs into the AC following the intracameral injection of Ag, (d) inhibited the induction of ACAID. ACAID is not induced in mice receiving an intracameral injection of anti-MCP-1 with Ag but did not influence the influx of monocytes into the AC.
Our results support the hypothesis that ACAID is a result of a response to ocular insult to the AC that recruits circulating F4/80+ cells that eventually recirculate and induce regulatory T cells in the thymus and spleen that effect ACAID.
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