Endogenous Cortisol and TGF-β in Human Aqueous Humor Contribute to Ocular Immune Privilege by Regulating Dendritic Cell Function

Abstract

Aqueous humor (AqH) has been shown to have significant immunosuppressive effects on APCs in animal models. We wanted to establish whether, in humans, AqH can regulate dendritic cell (DC) function and to identify the dominant mechanism involved. Human AqH inhibited the capacity of human peripheral blood monocyte-derived DC to induce naive CD4+ T cell proliferation and cytokine production in vitro, associated with a reduction in DC expression of the costimulatory molecule CD86. This was seen both for DC cultured under noninflammatory conditions (immature DC) and for DC stimulated by proinflammatory cytokines (mature DC). DC expression of MHC classes I/II and CD83 was reduced (mature DC only). Myeloid DC from peripheral blood were similarly sensitive to the effects of human AqH, but only under inflammatory conditions. The addition of α-melanocyte stimulating hormone and vasoactive intestinal peptide did not cause significant inhibition at physiological levels. However, the addition of exogenous cortisol at physiological levels recapitulated the AqH-induced reduction in CD86 and inhibition of DC-induced T cell proliferation, and blockade of cortisol in AqH partially reversed its suppressive effects. TGF-β2 had an additional effect with cortisol, and although simultaneous blockade of cortisol and TGF-β2 in AqH reduced its effectiveness, there was still a cortisol- and TGF-β–independent component. In humans, AqH regulates DC maturation and function by the combined actions of cortisol and TGF-β2, a pathway that is likely to contribute to the maintenance of immune privilege in the eye.

Prelabor cesarean delivery and early-onset acute childhood leukemia risk

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Can the Hair Follicle Become a Model for Studying Selected Aspects of Human Ocular Immune Privilege?

“…14,86 This phenomenon appears to be largely under the control of transforming growth factor (TGF)-␤, a key immunosuppressive cytokine in the aqueous humor. 61,62,87 In fact, in mice, a deficit of total TGF-␤2 in aqueous humor correlates with loss of ACAID. 51 These APCs then emigrate from the eye by traversing the trabecular meshwork (TM) and directly enter the blood stream to reach the spleen.…”

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