Aqueous humor contains transforming growth factor-beta and a small (less than 3500 daltons) inhibitor of thymocyte proliferation

Abstract

The anterior chamber of the eye is an immunologically privileged site in which allografts survive longer than at other body sites. In this regard, it is relevant that aqueous humor (AH) inhibits lymphocyte proliferation. In order to analyze AH for specific substances that inhibit thymocyte proliferation, samples of human AH, murine AH, and rhesus monkey AH were added to cultures of thymocytes stimulated by IL-1 or IL-2 in the presence of PHA. All samples of AH tested had potent inhibitory activity on thymocyte proliferation in this system. Inhibitory activity was lost by heating AH to 80 degrees C for 1 h. Dialysis of murine AH indicated that species smaller than 3500 Da were capable of mediating this activity; we have termed the factor(s) responsible for this "small inhibitory factor(s) of AH." Retentate, containing species larger than 3500 Da, retained inhibitory activity, but less than nondialyzed AH. Assays for PGE2 demonstrated that murine and human AH contained small quantities of PGE2. These quantities were insufficient to inhibit thymocyte proliferation in our assay system. Furthermore, AH from mice treatend with indomethacin had full inhibitory activity. Assays for transforming growth factor beta (TGF-beta) after acid activation demonstrated significant quantities of latent TGF-beta within human and murine AH which could be largely neutralized by antisera to TGF-beta. Active TGF-beta "activity" was also present without acid activation in samples of AH at a level approximately 20% that of latent TGF-beta. However, most of this "activity" could not be neutralized by antisera to TGF-beta. AH contains factors capable of limiting thymocyte proliferation.