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P. Hamrah, E. Bodek, H.J. Kaplan, N.S. Bora; Corneal Dendritic Cells Can be Actively Maintained in an Immature State by Soluble Factors in the Aqueous Humor . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5869.
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Dendritic cells (DCs) play a pivotal role in linking innate and adaptive immunity. Only mature DCs are able to initiate adaptive immune responses by sensitizing naive antigen–specific T cells. Recently, we have demonstrated that the central murine cornea is endowed with resident immature or precursor DCs that are MHC class II–negative. Factors preventing the maturation of corneal DCs are, so far, unknown. The purpose of this study was to investigate factors that maintain DCs in an immature state in the cornea.
Corneal stromal DCs were isolated from excised murine corneas under different culture conditions. Maturation of corneal DCs, both in serum containing media and in two different serum–free media was investigated. Further, different concentrations of bovine aqueous humor were added to these culture system to investigate the role of aqueous humor on maturation of corneal DCs. DC maturation was evaluated by immunocytochemistry and FACS analysis for presence of MHC class II and B7 co–stimulatory marker expression. Candidate immunosuppressive mediators were neutralized with blocking antibodies to identify specific factors.
Stromal DCs migrated during culture from explanted murine corneas. In media containing serum, a continuous increase in DC maturation with increased MHC class II and B7 costimulatory marker expression was observed. Addition of aqueous humor delayed and decreased MHC class II expression, but did not abolish the maturation of DCs. However, when corneal DCs were cultured in serum–free medium with aqueous humor there was complete suppression of DC maturation, with minimal MHC–class II and B7 costimulatory marker expression and a significant increase in survival time. Incubation with neutralizing antibodies to interleukin–6, but not prostaglandin E2 or TGF–ß, abrogated the inhibitory effect of aqueous humor on DC maturation.
These data demonstrate that monocytic DCs isolated from the central corneal stroma can be actively maintained in an immature state by factors present in the aqueous humor decreasing their T cell stimulating capacity. Moreover, we have developed a unique culture system allowing us to examine the effect of different soluble mediators on corneal DCs.
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