Somatostatin is an immunosuppressive factor in aqueous humor.
OBJECTIVE
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.
Taylor
Andrew W
AW
Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114, USA. awtaylor@vision.eri.harvard.edu
Yee
David G
DG
D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006728:Hormones / Q000032:analysis* / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000032:analysis* / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013004:Somatostatin / Q000032:analysis* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D000521:alpha-MSH / Q000096:biosynthesis
D006728:Hormones; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D013004:Somatostatin; D000521:alpha-MSH; D007371:Interferon-gamma