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Background It has been shown experimentally in rodents that removal of the spleen leads to increased rejection of corneal allografts after corneal transplantation (keratoplasty). Case presentation Here, we report a unique case of a splenectomized patient with corneal endothelial dystrophy who underwent posterior lamellar keratoplasty. During follow-up of 4 years, we did not detect any signs of corneal allograft rejection. Conclusions Our report indicates that an intact spleen is not necessary for allograft acceptance after posterior lamellar keratoplasty. To the best of our knowledge, this is the first report of a splenectomized patient receiving a (lamellar) corneal transplant.

International audience; Anterior chamber-associated immune deviation (ACAID) is a well-known phenomenon that can occur after an antigen is introduced without any danger signal into the anterior chamber of a murine eye. It is reported to lead to an antigen-specific immune deviation throughout the body. Despite the relatively little evidence of this phenomenon in humans, it has been suggested as a potential prophylactic strategy in allograft rejections and in several autoimmune diseases. Cellular and molecular mechanisms of ACAID have been explored in different murine models mainly as proofs of concept, first by direct analyses of immune components in normal immunocompetent settings and by cell transfer experiments. Later, use of knockout (KO) mice has helped considerably to decipher ACAID mechanisms. However, several factors raise questions about the reliability and validity of studies using KO murine models. This mini-review summarizes results obtained with KO mice and discusses their advantages, their potential weaknesses, and their potential methods for further progress.

When allogeneic P815 mastocytoma cells (derived from DBA/2 mice) are injected into the anterior chamber of the eyes of BALB/c mice, they take advantage of the immunologic privilege within this site...

Anterior chamber-associated immune deviation (ACAID) is a systemic form of tolerance that is elicited by introducing antigens into the anterior chamber of the eye. ACAID is characterized by deficiencies in delayed-type hypersensitivity and complement-fixing antibodies upon subsequent challenge with antigen. The mechanisms responsible for the generation of this form of tolerance are not yet completely clear. Here we asked whether gammadelta T cells, which are critical in the induction of oral tolerance and nasal tolerance, play a role in ACAID. The percentage of splenic gammadelta T cells was higher in mice that received antigen via the anterior chamber compared to untreated mice. In addition, CD44 was up-regulated on some splenic gammadelta and alphabeta T cells after the intraocular injection of antigen. Moreover, administration of antigen into the anterior chamber did not induce ACAID in the C57BL/6 mice pretreated with anti-mouse delta-chain monoclonal antibody or in the gammadelta T-cell-receptor-deficient (delta-/-) mice. gammadelta T cells from wild-type mice reconstituted ACAID when transferred into the delta-/- mice before injection of antigen, verifying that the deficiency in delta-/- mice results from the lack of gammadelta T cells rather than from an inadvertent change caused by deletion of the delta-chain. These findings indicate that gammadelta T cells play a very important role in ocular tolerance.

Immuno-ophthalmology evolved during the 20th century as a subspecialty linking ophthalmologists and immunologists. This emerging subspecialty has focused on the use of immunology to better understand and treat ocular disorders. To help the allergist/clinical immunologist better appreciate the growing field of immuno-ophthalmology, this 2-part review series (Part II: Ocular Allergy will appear in the December issue of the Journal) will provide an overview of the impact that immunology has had on our understanding and treatment of allergic and immunologic eye diseases. The current review will focus on mechanisms by which mast cells, T cells, eosinophils, cytokines, and other inflammatory constituents contribute to the unique features of eye disease and their link to allergic responses that occur in other organs of the body.

Anterior chamber-associated immune deviation (ACAID) is characterized by the systemic inhibition of delayed type hypersensitivity (DTH) reactions to antigens which have previously been placed into the anterior chamber of the eye. Since its initial characterization, ACAID has been elicited to a wide variety of antigens, including alloantigens, and has been shown to be due to the immune deviating effects of factors such as transforming growth factor beta (TGF-s) in the aqueous humor on ocular antigen-presenting cells (APCs). ACAID can also be induced by injecting animals with nonocular APCs, such as peritoneal exudate cells (PECs), which have been precultured with TGF-s and antigen in vitro. The objective of this study was to determine whether alloantigenic ACAID can be effective in preventing the rejection of rat islet allografts. The notion that islet allograft rejection can be inhibited by ACAID stems from an early study showing an ACAID-induced delay in the rejection of skin grafts. Furthermore, the imm...

We investigated the induction of anterior-chamber-associated immune deviation (ACAID) by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Two strains of HSV-1 (VR-3 and F) and four strains of HSV-2 (UW-268, 186, SL, and MS) were inactivated with ultraviolet light, and the anterior chamber of BALB/c mice was inoculated with a viral strain. Immunization against delayed-type hypersensitivity (DTH) was done subcutaneously on day 7 after anterior chamber inoculation. On day 10 after DTH immunization, each virus was inoculated into the foot pad. DTH was evaluated by measuring the foot pad thickness at 24 h after the inoculation into the foot pad. DTH was suppressed by anterior chamber inoculation with more than 10(3) plaque-forming units (PFU) of the VR-3, UW-268, 186, and SL strains, and with 10(5) PFU of the F strain, but not by the MS strain. Until now, HSV-2 was believed not to induce ACAID, however, our results indicate that some HSV-2 strains induce ACAID.ACAID induction by HSV-1 and HSV-2 may depend on both the viral strain and the amount of ocular viral antigen.

The eye is a unique place for the development of an immune response. Beyond the usual mechanisms of immune restraint, the eye evolved with its exclusive mechanisms such as anterior chamber associated immune deviation. Therefore, immune-mediated inflammation in the eye does not develop at the same pace as in other sites of the body. Here we will address such peculiarities as they regard to ocular autoimmunity, using the experimental autoimmune uveitis as a model to understand the participation of cytokines in the process of aggression against the eye, as well as their immunoregulatory role.

Evidence of ocular immune privilege was noted almost 130 years ago. The past 30 years have witnessed an explosion in research on ocular immune privilege. One of the primary mechanisms that contribut

Murine macrophages treated with TGF-beta2 are capable of inducing anterior chamber-associated immune deviation (ACAID), and these macrophages are characterized by impaired IL-12 production and CD40 expression, consequently failing to promote Th1 cell differentiation. In this study, we investigated whether human monocytes can also acquire the specific functions by TGF-beta2 treatment, even when the monocytes are isolated from patients with Behcet's disease (BD). Adherent monocytes isolated from peripheral blood mononuclear cells (PBMC) of 16 BD patients and 16 healthy controls, were cultured overnight with or without 5 ng/ml of TGF-beta2. Then, TGF-beta2-treated or untreated adherent cells were co-cultured with allogeneic CD4(+) T cells obtained from healthy subjects. TGF-beta2 treatment inhibited the abilities of adherent monocytes obtained from BD patients to stimulate the proliferation and IFN-gamma production of allogeneic CD4(+) T cells. The reduced IFN-gamma production was also confirmed by IFN-gamma mRNA expression in the co-cultured T cells. IL-12 production and CD40 molecule expression by adherent monocytes obtained from BD patients were strikingly reduced by TGF-beta2 treatment. These results suggest a possibility that adherent monocytes isolated from BD patients may acquire a property to induce ACAID by treatment with TGF-beta2.

Immune privilege was first explored in the late 1800s by van Dooremaal, and was then extended by Medawar in the mid 1900s to fit in with emerging concepts of transplantation immunology. Modern concepts and understanding of immune privilege come from subsequent studies produced by Medawar, Billingham, and Streilein. The exploitation of the model of anterior chamber immune deviation (ACAID) in mice has allowed us to look at both cellular and molecular mechanisms involved in the prevention of potentially damaging immune responses in such privileged sites. This review gives a historical perspective of the immune privilege research and provides up-to-date information of molecules, cells, and concepts newly recognized as contributing to tolerance induction induced in such specialized areas of the body. Evidence is given to support the idea that application of such information may lead to potential for therapeutic applications of ACAID mechanisms in prevention of progression of immune-inflammatory diseases in humans.

To determine the extent to which proinflammatory cytokines [(interleukin-I-beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), gamma-interferon (gamma-IFN)] interfere with induction of anterior chamber-associated immune deviation (ACAID).Proinflammatory cytokines were injected intracamerally prior to local injection of ovalbumin (OVA), or added to cultures containing peritoneal exudate cells (PEC), transforming growth factor-beta (TGF beta), and OVA. After incubation, these cells were washed and injected intravenously into naive, syngeneic mice. One week later, the mice were immunized with OVA in adjuvant, and delayed hypersensitivity (DH) was assessed seven days later.Eyes pretreated with IL-1 beta, TNF alpha or gamma-IFN failed to support ACAID induction. In addition, IL-1 beta and gamma-IFN robbed OVA-pulsed, TGF beta-treated PEC of their ability to induce ACAID, whether the inflammatory cytokines were added prior to, simultaneously with, or after exposure to TGF beta. By contrast, in-vitro exposure of PEC to TNF alpha was unable to prevent TGF beta-promoted ACAID.IL-1 beta, gamma-IFN, and TNF alpha injected intracamerally rob the eye of immune privilege and prevent ACAID induction. In the cases of IL-1 beta and gamma-IFN, ACAID seems to be prevented by a direct action of the cytokines on antigen-presenting cells (APCs). In the case of TNF alpha, prevention of ACAID in vivo probably occurs by an APC-independent mechanism.

Corneal allograft rejection is a major cause of graft failure. Identifying possible risk factors for rejection may improve chances for successful outcome. We report three cases of graft rejection associated with the use of post-operative pilocarpine at different concentrations. Pilocarpine was used to treat persistent epithelial defects or raised intraocular pressure. The patients were managed until their rejection episodes resolved. In each case, graft rejection ensued in a quiet eye after initiating treatment with pilocarpine, without other change in medications. Each graft rejection episode resolved with discontinuation of pilocarpine and administration of prednisolone acetate. We propose that if pilocarpine does indeed diminish corneal allograft immune privilege and enhance graft rejection, the mechanisms may include induced intraocular inflammation and altering of anterior chamber associated immune deviation. This is the first report implicating a topical ophthalmic medication with possible corneal allograft rejection.

Alloantigens placed into the anterior chamber of the eye elicit antigen-specific suppression of systemic delayed-type hypersensitivity (DTH) responses and severe impairment of skin allograft rejection. This pattern of immunological impairment has been termed anterior-chamber-associated immune deviation (ACAID). We have previously proposed that ACAID is the underlying mechanism responsible for immunologic privilege within the anterior chamber of the eye. The present study examined the role of interleukin 2 (IL-2) in the induction of ACAID. As previously shown, intracameral inoculation of P815 cells into allogeneic BALB/c recipients resulted in antigen specific suppression of DTH responses. However, subcutaneous administration of recombinant IL-2 along with intracameral inoculation of P815 cells prevented ACAID and permitted the development of positive DTH responsiveness in BALB/c hosts. In order to abrogate ACAID, exogenous IL-2 was required only during the first 72 hr following anterior chamber presentation of alloantigens. Collectively, the results indicate that induction of ACAID and the antigen-specific suppression of systemic DTH responses are due to IL-2 deficiency during the early stages of antigen perception. This in turn implies that the immunological privilege within the anterior chamber of the eye may pivot on the deficiency of a single lymphokine, interleukin 2.

Herpes simplex virus Type 1 (HSV-1) inoculated intracamerally (IC) into the anterior chamber of BALB/c eyes induces anterior chamber associated immune deviation (ACAID) in which T cell-mediated delayed type hypersensitivity (DTK) responses to HSV-1 are impaired while B cell-mediated anti-HSV neutralizing antibody responses are intact or enhanced.