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PURPOSE: To detect the presence of somatostatin (SOM) in normal aqueous humor and to characterize its immunosuppressive activity. METHODS: Fresh rabbit aqueous humor was assayed for SOM by competitive ELISA. Primed T cells stimulated through their T-cell receptor (TCR) were treated with SOM at concentrations that ranged the level of SOM found in normal aqueous humor. The T cells were assayed for proliferation, lymphokine production, and immunosuppressive activity. RESULTS: Normal rabbit aqueous humor contained 196 ± 45 pg/m (10-10 M) of SOM. At concentrations between 10 and 300 pg/ml, SOM suppressed IFN-gamma production by TCR-stimulated primed T cells in culture. Frozen and thawed aqueous humor depleted of SOM no longer suppressed IFN-γ production by the TCR-stimulated primed T cells. SOM induced TGF-β but not IL-4 production, nor did it suppress proliferation by TCR-stimulated primed T cells. The SOM-treated T cells functioned as regulatory T cells, and this regulatory activity was neutralized by anti-α-MSH antibodies. Furthermore, SOM induced α-MSH production by the TCR-stimulated primed T cells. CONCLUSIONS: SOM is present in aqueous humor and contributes to the immunosuppressive activity of aqueous humor. Moreover, SOM induces the production of the potent immunomodulating factor α-MSH by TCR-stimulated primed T cells through which the SOM-treated T cells suppress other T cells. Thus, SOM can contribute to the ocular immunosuppressive microenvironment by promoting the production of immunosuppressive cytokines and inducing the activation of regulatory T cells.
Dr. A.W. Taylor, Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA. awtaylor@vision.eri.harvard.edu
2.6.3 Compostion (Part of: 2 Anatomical structures in glaucoma > 2.6 Aqueous humor dynamics)