Delayed hypersensitivity (DH), the prototypical form of cell-mediated immune responsiveness, is mediated with the participation of considerable nonspecific inflammation which necessarily disrupts the anatomic integrity of involved and adjacent tissues. Damage of this type is of minor consequence to many visceral and cutaneous organs, but is of devastating consequence for organs such as the eye and the brain. At least in the case of the eye, the organ is remarkably adept at regulating the immune system's ability to respond to intraocular antigens by selectively down-regulating both the induction and expression of delayed hypersensitivity while leaving other effector modalities intact. This ability of the eye to selectivity down-regulate systemic DH responses to intracamerally inoculated antigens is known as anterior chamber-associated immune deviation (ACAID) and is mediated in part by antigen-specific regulatory T cells. Recent work suggests that macrophages (M phi) that reside in the iris and ciliary body can migrate out of an antigen-bearing eye and activate regulatory T cells within the spleen. In an effort to understand the mechanism by which intraocular M phi interact with antigen in the anterior chamber of the eye (AC) and subsequently induce splenic regulatory cells in ACAID, we have investigated what role, if any, the AC microenvironment itself plays in ACAID induction. The results reveal that CD45- parenchymal iris/ciliary cells secrete a soluble factor(s) locally and into the aqueous humor which endows resident, mature M phi with ACAID-inducing capabilities. Mice receiving infusions of these altered, antigen-pulsed M phi are incapable of mounting a significant DH response following immunization with antigen in adjuvant. Importantly, the ACAID-inducing effect is achieved when conventional, extraocular M phi are exposed in vitro to a soluble factor present in aqueous humor or culture SN from iris and ciliary body cells. Further investigations into the identity of this factor reveal it to be transforming growth factor-beta (TGF-beta). The role of TGF-beta in the generation of ACAID, as well as the implications of these findings to an understanding of immunologic privilege in general, are discussed.

The eye, brain, and fetoplacental unit within the pregnant uterus are immunologically privileged sites that contain unique fluids with suspected immunoinhibitory properties. Aqueous humor, which is normally present within the anterior chamber (AC) of the eye, has been shown to suppress antigen-driven T cell activation, and to contain significant amounts of transforming growth factor beta-2 (TGF-beta). Antigens injected into the AC of normal mice induce a deviant form of systemic immunity, termed anterior chamber-associated immune deviation (ACAID), which is characterized by a selective inability to display antigen-specific delayed hypersensitivity. It has recently been reported that eye-derived macrophages appear in the blood following AC injection of a soluble antigen, and that these cells can induce antigen-specific ACAID when injected into naive, syngeneic recipients. Moreover, antigen-pulsed peritoneally derived macrophages that are exposed in vitro to aqueous humor, supernatants of cultured iris and ciliary body cells (I/CD), or TGF-beta have been found to assume ACAID-inducing properties. In the present experiments, amniotic fluid and cerebrospinal fluid from mice, rats and humans, as well as supernatants from cultured I/CB cells, have been examined for their capacity to confer ACAID-inducing properties on peritoneal macrophages. It was found that each of these biologic fluids, but neither normal mouse serum nor rat thoracic duct lymph, was able to endow antigen-pulsed peritoneal macrophages with ACAID-inducing properties. Moreover, fluids from these immune privileged sites were found to contain latent and/or active TGF-beta, as determined by bioassay, using neutralizing anti-TGF-beta antibodies. It is concluded (a) that the immune privileged states of the eye, the brain, and the fetoplacental unit share common features, and possess unique fluids with a similar capacity to force macrophages to present antigens in a "deviant" manner and (b) that this capacity is mediated, at least in part, by TGF-beta. These results are discussed in terms of the potential physiologic and pathophysiologic significance of immune privilege in these three specialized tissues.

No author has a financial or proprietary interest in any material or method mentioned.

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We would like to call attention to a phenomenon of calcification of various hydrophilic acrylic intraocular lenses (IOLs) following procedures using intracameral injections of gas. Calcification is localized to the anterior surface/subsurface of the IOL and within the pupillary area. Poor quality of vision through the opacification has required IOL exchange in several cases. The explanted IOLs were analyzed by us and others.Saeed et al. 1 described a case in which sulphur hexafluoride and later perfluoropropane gas was used intracamerally to manage large iatrogenic Descemet membrane detachments observed during cataract surgery. A few weeks later, a fine haze was observed under the anterior surface of the hydrophilic acrylic IOL. Details on the aspect or nature of the IOL opacification were, however, not available in the report. Three cases of calcification of hydrophilic acrylic IOLs associated with intraocular injection of gas were recently compiled by Dhital et al. 2 The explanted IOL from one of those cases was analyzed in our laboratory. The patient, who had a history of Fuchs endothelial corneal dystrophy, had phacoemulsification with implantation of a hydrophilic acrylic IOL combined with Descemet-stripping automated endothelial keratoplasty (DSAEK) in February 2007, with subsequent intracameral injections of air and gas. The DSAEK was repeated in August 2007 with a complete gas fill of the anterior chamber. Approximately 1 month later, a central circular area of IOL opacification was noted. In the other 2 cases, IOL opacification was observed after intracameral injection of gas to control hypotony following trabeculectomy and after vitrectomy with cryotherapy and intravitreous injection of gas in an eye with a history of blunt trauma, respectively. The 3 cases by Dhital et al. 2 shared a distinctive pattern of opacification limited to the anterior surface and/or subsurface of the IOL and defined by the pupillary margin. The calcific nature of the deposits observed within the area of opacification was confirmed by histochemical staining and scanning electron microscopy coupled with energy-dispersive x-ray spectroscopy. 2 Our laboratory has recently analyzed another similar case of localized IOL calcification following DSAEK. The patient had Fuchs dystrophy and had had uneventful phacoemulsification with hydrophilic acrylic IOL implantation in June 2010. Descemetstripping automated endothelial keratoplasty with intracameral injections of air was performed in October 2010. Two months later, the patient complained of "foggy" vision. Opacification of the anterior surface of the IOL within the pupillary area was observed. Figure 1. Case of localized hydrophilic acrylic IOL opacification after DSAEK, leading to explantation. A: Clinical photograph taken after pupil dilation. The arrows delineate the area of opacification, which is denser in the upper right quadrant. B: Gross photograph of the IOL, which was bisected for explantation. C: Light photomicrograph of the explanted IOL showing the presence of deposits o...