J Y Niederkorn

..These results indicate that IFN-? is not needed for the induction of CD8+ ACAID Tregs but is required for ACAID Tregs to exert the suppression of allospecific DTH responses...

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..To determine the role of tumor necrosis factor receptors (TNFRs) in corneal allograft rejection...

..It remains to be ascertained if immune stimulation affects the malignancy of ocular tumors, but it represents an intriguing explanation for the paradoxes of uveal melanoma...

..Ocular immune privilege was originally perceived as a simple anatomic anomaly that has evolved to be one of the most sophisticated and intriguing forms of immune regulation...

..Either CD8+ or CD8 T cells can produce corneal allograft rejection, however functional FasL is necessary for optimal rejection, even in a high-risk setting...

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..A growing body of evidence from rodent studies suggests that a breakdown in immune privilege contributes to multiple sclerosis, uveitis, corneal allograft rejection and possibly even immune abortion...

..At least four different pathways exist for the development of ocular Treg cells. The redundancy in the generation of T reg cells is a testament to their importance in restricting intraocular inflammation and preserving vision...

..CD8(+) T regs can produce suppression directly by killing immune cells or indirectly by co-opting other cells to elaborate end-stage suppressive molecules such as TGF-beta, IL-10, and indoleamine dioxygenase (IDO)...

..The availability of gene knockout mice and the wealth of monoclonal antibodies have permitted exquisite dissection of the pathophysiology and immune regulation of allergic conjunctivitis...

..Thus, Th2-based allergic diseases significantly reduce the immune privilege of the corneal allograft and represent important risk factors for consideration in the atopic patient...

..To date, tumors seem to be winning this arms race, but an increased understanding of these mechanisms should provide insights for designing immunotherapy that was envisioned over half a century ago, but has failed to materialize to date...

..It is widely believed that immune privilege is an adaptation for reducing immune-mediated injury to ocular cells that have limited or no capacity for regeneration...

..Thus, exacerbation of corneal allograft rejection in mice with AC is associated with a mixed Th1 and Th2 alloimmune response, and the contribution of Th1 cells is through their production of IFN-gamma...

..Recent studies have examined new strategies for restoring immune privilege to such high-risk hosts...

..However, certain conditions create high risks for immune rejection. This review discusses recent insights into the mechanisms that rob the corneal allograft of its immune privilege...

..Together, our findings suggest new strategies to successfully eliminate ocular tumors while preserving the integrity of the eye...

..Strategies to re-establish corneal immune privilege may have clinical application for high-risk hosts who have rejected previous corneal allografts...

..Thus, immune privilege is a crucial adaptation for preserving vision...

..The beauty of this mechanism lies in its exquisite simplicity and efficacy...

..This study examined the role of Th1 and Th2 cytokines, accessory cells, and lymphoid organs that are known to be instrumental in other forms of antigen-specific tolerance...

..Gaining a better understanding of the immune privilege of the hair follicle may provide insights into the regulation and pathogenesis of immune-mediated diseases of the skin...

..The prevalence of serum immunoglobulin G (IgG) and tear IgA against three species of Acanthamoebawas assessed in healthy subjects and patients with Acanthamoebakeratitis...

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..Thus, gamma delta T cells are needed for sustaining at least one aspect of ocular immune privilege and for promoting corneal allograft survival...

..To characterize the role of B cells in the induction of anterior chamber-associated immune deviation (ACAID)...

..This study sought to test the hypothesis that CTLs are essential in promoting corneal graft rejection...

..CONCLUSION: FasL-induced apoptosis of hepatocytes in contact with FasL-positive human uveal melanoma cells may contribute to hepatic failure during metastatic disease...

..CONCLUSIONS: Alloantibody, although not necessary for corneal graft rejection, can produce extensive injury to corneal allografts in a complement-dependent manner...

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..These results suggest that peripheral tolerance induced through the eye requires Ag-presenting B cells that simultaneously present Ags on both MHC class I and II molecules...

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..This demonstrates that macrophage and CD4+ T-cell co-operation is needed for non-phthisical rejection of intraocular tumours...

..The CD8 T cells represent a unique DN T cell population that might mediate rejection by either direct cytolysis or by inducing apoptosis of the donor corneal endothelium...

..These findings demonstrate that IL-17A is not required for corneal allograft rejection and may instead contribute to the immune privilege of corneal allografts...

..Although the presence of donor-specific LCs greatly jeopardises corneal allograft survival, migration of host-derived LCs into corneal allografts does not appear to increase the risk of rejection...

..However, the widespread use of rodent models of orthotopic corneal transplantation has shed new light on the pathogenesis of corneal graft rejection...

..Thus, MHC matching may reduce the risk of corneal graft rejection in patients with atopic keratoconus...

..Taken together, these findings suggest that IL-17 has a role in corneal epithelial barrier disruption in DE...

..Thus, TGF-beta predisposes ocular APC to secrete IL-10 during Ag processing. This, in turn, directs the immune response away from a Th1 pathway and toward a Th2-like response in which DTH is suppressed...

..The objective of this study was to evaluate the severity of corneal epithelial disease and T-cell cytokine profile in the ocular surface tissues of CD25KO mice...

..CLINICAL RELEVANCE: Manipulation of apoptosis regulatory proteins, such as survivin, may have therapeutic applications in the management of uveal melanomas...

..The findings also reveal that some IFN-gamma-independent tumor rejection processes are excluded from the eye and may represent a new facet of ocular immune privilege...

..These results underscore the importance of the innate immune apparatus in the resistance to Acanthamoeba keratitis...

..Finally, the CD4+ afferent T suppressor cells are not natural killer T cells, but do express the CD25 cell surface marker...

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..Although the corneal endothelium is highly susceptible to Fas-induced apoptosis, this is apparently not the primary mechanism of CD4(+) T-cell-dependent rejection...

..To our knowledge, this is the first study to report that B-cell proliferation is needed for B-cell-induced T-cell tolerance...

..Several novel therapeutic strategies hold promise for modulating the alloimmune response by either promoting antigen-specific tolerance or redirecting the host's response from a Th1 pathway toward a Th2 pathway...

..To assess the expression of PD-L1 on human uveal melanomas and its potential to suppress T-cell function...

..The results indicate that CD8+ T cells circumvent immune privilege and mediate intraocular tumor rejection by a TNF-alpha-dependent manner while leaving the eye intact and vision preserved...

..To investigate the role of interferon (IFN)-gamma in the pathogenesis of conjunctival squamous metaplasia in dry eye...

..The results emphasize the importance of maintaining adequate amebicidal therapy if a topical steroid is used in the management of Acanthamoeba keratitis...

..To assess the expression of PD-L1 and PD-L2 on human ocular cells and their potential to regulate ocular inflammation...

..Moreover, AEC supernatant inhibited macrophage migration in vitro. CONCLUSIONS: AECs secrete soluble factors that inhibit cells in both the innate and adaptive immune systems...

..Moreover, pharmacological agents and biological response modifiers that independently display antineoplastic properties can enhance TRAIL-induced apoptosis in resistant uveal melanoma cells...

..The results also suggest that exogenous angiostatin may have potential therapeutic implications in the management of patients with primary intraocular melanomas...

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..Moreover, the contribution of gammadelta T cells ACAID generation could be replaced by adding exogenous recombinant mouse IL-10 to ACAID spleen cell cultures lacking gammadelta T cells...

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..To determine whether blocking the expression of the chemokine receptor CXCR4 using siRNA inhibits chemotactic responses of human uveal melanoma cells to liver-derived factors and prevents liver metastases...

..The results indicate that the MIP-133 protein modulates MMP-2 and -3 expression differently in human corneal epithelial and stromal cells...

..A Cfh variant (Y402H) increases the risk for AMD. The purpose of this study was to develop a pathophysiologically relevant animal model of AMD based on this genetic risk factor...

..The goal of the present study was to gain insight into the pathogenicity of Acanthamoeba infection as well as to determine whether oral immunization with aPA and MIP-133 produce an additive protection against Acanthamoeba keratitis...

..05). Killing was inhibited by cytochalasin D, but not by L-N6-1-iminoethyl-L-lysine dihydrochloride (L-NIL), which is a selective inhibitor of inducible NO synthase (INOS)...

..To determine the expression of the chemokine receptors CXCR4 and CCR7 on human uveal melanoma cells and their metastases and the effect of liver-borne factors on the chemotactic responses of uveal melanoma cells...

..The results from this study suggest that IFN-gamma inducible IDO upregulation by primary and metastatic uveal melanoma may generate a local immune privileged microenvironment to promote escape from T cell-mediated immune surveillance...

..CONCLUSIONS: The results support the feasibility of activation of NK cell function through gene transfer as one possible therapeutic strategy for reducing hepatic metastases of uveal melanomas...

..Targeting such proteases could lead to the development of vaccines that target the disease process rather than the pathogen itself...

..Macrophages killed the cysts by phagocytosis, whereas neutrophils killed cysts through the secretion of MPO...

..The innate immune apparatus is crucial for the resolution of the disease. With the exception of mucosal antibody, elements of the adaptive immune system fail to prevent infection or contribute to its resolution in experimental animals...

..These data indicate that resistance of some uveal melanoma cells to cisplatin-induced apoptosis is controlled by anti-apoptotic proteins, such as survivin, that are sensitive to actinomycin D treatment...

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..Oral immunization with MIP133 mitigates Acanthamoeba keratitis and demonstrates the feasibility of antidisease vaccines for pathogens that resist immune elimination...

..Finally, IFN-?, and IL-17A, which were normally viewed as proinflammatory, exert the opposite effect in the context of corneal transplantation and are necessary for corneal allograft survival...

..In still other cases, the immune response is all but silenced. These immunological adjustments are the basis for regional immunity and immune-privileged sites...

..To characterize the effect of repeated topical exposure to allergen in a mouse model of allergic conjunctivitis and to determine the role of interferon-gamma (IFN-gamma) in the pathogenesis of allergic conjunctivitis...

..The objective of this article is to highlight the importance of understanding the exact mechanisms of Th1 and Th2 cells in the pathology of ocular allergy...

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..This is especially noteworthy, as no existing therapeutic modality prevents metastasis of uveal melanoma or prolongs the survival of patients with uveal melanoma...

..Extensive evidence suggests that the eye and the fetus employ similar strategies for establishing immune privilege for preserving vision and the unborn respectively...

..g., corneal transplantation). In some cases, it may be desirable to abrogate immune privilege to promote the immune-rejection of sight- and life-threatening ocular neoplasms. ..

..These studies will lead to improved strategies for re-establishing immune privilege of corneal transplants and offsetting the untoward effects of allergic diseases on the fate of corneal transplants. ..

..g., corneal transplantation) or abrogate immune privilege to protect against sight- and life-threatening neoplasms. ..

..Both strategies procure antigen-specific suppression of host immune responses and should prove useful in preventing corneal graft rejection. ..

..g., corneal transplantation). In some cases, it may be desirable to abrogate immune privilege to promote the immune-rejection of sight- and life-threatening ocular neoplasms. ..

..The long rang goal of this project is to design, develop, and evaluate novel immunotherapeutic modalities for the prevention and treatment of uveal melanoma metastases. ..

..All three of these aims will be addressed in a well-characterized mouse model of penetrating keratoplasty. ..

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..The fourth aim will evaluate the therapeutic efficacy of a monoclonal antibody directed against human CD54 in controlling liver metastases in a nude mouse model of uveal melanoma. ..

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..These studies will lead to improved strategies for re-establishing immune privilege of corneal transplants and offsetting the untoward effects of allergic diseases on the fate of corneal transplants. ..

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..The fourth aim will evaluate the therapeutic efficacy of a monoclonal antibody directed against human CD54 in controlling liver metastases in a nude mouse model of uveal melanoma. ..

..The results from these investigations should provide important insights into the immunobiology of corneal allografts and the feasibility of specific immunological strategies for promoting corneal allograft survival...

..Understanding immune privilege may lead to strategies for promoting long term survival of therapeutic organ grafts...

..The long range goals of this project are to understand immune regulatory processes in the eye and to manipulate such processes to reduce immune-mediated injury and corneal graft rejection...