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Somatostatin is an immunosuppressive factor in aqueous humor
1Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114, USA. awtaylor@vision.eri.harvard.edu
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/mL (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-gamma production by the TCR-stimulated primed T cells. SOM induced TGF-beta 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-alpha-MSH antibodies. Furthermore, SOM induced alpha-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 alpha-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.