NKT cell exacerbation of liver metastases arising from melanomas transplanted into either the eyes or spleens of mice.

Purpose: To explore the role of natural killer T (NKT) cells in the development of liver metastases in mice harboring intraocular melanomas.

Methods: Cells derived from the cutaneous B16 melanoma cell line (B16LS9) were transplanted either into the vitreous body or under the spleen capsules of wild-type C57BL/6 mice and NKT-cell-deficient Jα18(-/-) and CD1d(-/-) mice. The development of liver metastases was evaluated by histopathology.

γδ T cells are required for maximal expression of allergic conjunctivitis.

Purpose: To determine the function of γδ T cells in early- and late-phase responses in allergic conjunctivitis.

Methods: Wild-type (WT) C57BL/6 and γδ T cell-deficient (TCR-δ(-/-)) mice were immunized intraperitoneally and challenged topically for 7 consecutive days with short ragweed pollen. Natural killer T (NKT) and γδ T cell-double-deficient mice were generated by treating TCR-δ(-/-) mice with anti-CD1d antibody.

NKT cells are necessary for maximal expression of allergic conjunctivitis.

Allergic conjunctivitis (AC) is elicited by immediate hypersensitivity responses to environmental agents. It is initiated by a T(h)2-dominated immune response that is characterized by production of IgE antibodies and eosinophilic infiltration. By using an experimental mouse model of AC induced by short ragweed (SRW) pollen, we show that sensitized Jalpha18(-/-) mice, which lack type I NKT cells, and CD1d(-/-) mice, which lack type I and type II NKT cells, exhibited a decrease in tearing, lid edema, conjunctival edema and vasodilatation and eosinophil infiltration into the conjunctiva when compared with wild-type (WT) mice in both T(h)1- and T(h)2-prone hosts (C57BL/6 and BALB/c mice, respectively).

Allergic conjunctivitis exacerbates corneal allograft rejection by activating Th1 and th2 alloimmune responses.

Allergic conjunctivitis (AC) and airway hyperreactivity exacerbate corneal allograft rejection. Because AC and airway hyperreactivity are allergic diseases of mucosal tissues, we determined whether an allergic disease of a nonmucosal tissue would affect corneal allograft rejection and whether Th2 cells alone accounted for accelerated graft rejection in allergic mice. Hosts sensitized cutaneously with short ragweed pollen developed cutaneous immediate hypersensitivity but rejected corneal allografts at the same tempo and incidence as naive mice.

Uveal melanoma expression of indoleamine 2,3-deoxygenase: establishment of an immune privileged environment by tryptophan depletion.

The enzyme indoleamine 2,3-dioxygenase (IDO) catalyzes degradation of tryptophan, an essential amino acid required for lymphocyte activation and proliferation. Many tumors express IDO which implies that it acts as a mechanism to evade T cell-mediated immune attack, and also to establish an immunosuppressive tumor microenvironment. The purpose of this study was to determine whether primary and metastatic uveal melanoma expressed the IDO gene and whether uveal melanoma cells could deplete tryptophan.

CD4+ T-cell-independent rejection of corneal allografts.

Background: Several studies suggest that a significant number of corneal allografts undergo rejection in the absence of CD4 T cells. This study examined the role of CD4 T cell-independent mechanisms of corneal allograft rejection.

Methods: BALB/c corneal allografts were transplanted to C57BL/6 beige nude mice that received either CD8 or CD8 T cells from C57BL/6 CD4 knockout (KO) mice that had rejected BALB/c corneal allografts.

Cutting edge: atopy promotes Th2 responses to alloantigens and increases the incidence and tempo of corneal allograft rejection.

A large body of evidence suggests that corneal allograft rejection is mediated by a type 1 Th cell response and that deviation toward type 2 immunity favors graft survival. However, clinical observations indicate that patients with severe ocular allergies have increased risk of corneal allograft rejection. We used a mouse model of atopic conjunctivitis to evaluate the effects of Th2 immune deviation on corneal allograft survival and possible mechanisms of graft rejection.

Immunosuppressive factors secreted by human amniotic epithelial cells.

Purpose: Amniotic membrane has been applied to the ocular surface to restore corneal function. The beneficial effect of amniotic membrane transplantation may be due to the immunosuppressive effects of amniotic epithelial cells. The purpose of this study was to determine whether amniotic epithelial cells (AECs) secrete anti-inflammatory and antiproliferative factors that affect the chemotaxis of neutrophils and macrophages and suppress both T- and B-cell proliferation in vitro.

CD4(+) T-cell-mediated mechanisms of corneal allograft rejection: role of Fas-induced apoptosis.

Background: The role of CD4(+) T cells as effector cells in corneal allograft rejection is poorly understood. We investigated the role of CD4(+) T cells as helper cells in the generation of allospecific effector macrophages in corneal graft rejection and the role of CD4(+) T cells as apoptosis-inducing effector cells.

Methods: Corneal allografts were transplanted to CD4 knockout, FasL-deficient, and macrophage-depleted hosts.

Expression and possible function of IL-2 and IL-15 receptors on human uveal melanoma cells.

Purpose: Interleukin-2 (IL-2) and IL-15 receptors have been detected on some murine neoplasms. Accordingly, the expression of these receptors on human uveal melanoma cell lines was examined, and the effect of exogenous IL-2 and -15 on melanoma cell proliferation, susceptibility to natural killer (NK) cell-mediated cytolysis, and sensitivity to apoptosis were assessed.

Methods: Nine human uveal melanoma cell lines and three cell lines from uveal melanoma metastases were tested by flow cytometry for the expression of human IL-2R and -15Ralpha.

Role of tumor necrosis factor receptor expression in anterior chamber-associated immune deviation (ACAID) and corneal allograft survival.

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

Methods: Corneal epithelial and endothelial cells were examined by flow cytometry for the expression of TNFRI and TNFRII and their susceptibility to TNF-alpha-induced apoptosis. Corneal allografts from normal and TNFRI and TNFRII knockout (KO) C57BL/6 mice were transplanted to BALB/c hosts, and the fate of the allografts was monitored.

Fate of MHC-matched corneal allografts in Th1-deficient hosts.

Purpose: To determine whether the Th1 cytokine, interferon (IFN)-gamma, is necessary for corneal graft rejection.

Methods: Full-thickness penetrating keratoplasties were performed in normal mice and in IFN-gamma knockout (KO) mice.

Results: Sixty-four percent of the MHC-mismatched corneal allografts were rejected in IFN-gamma KO mice.

Uveal melanoma expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors and susceptibility to TRAIL-induced apoptosis.

Purpose: The study had two purposes: to examine the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors on uveal melanoma cells and metastases arising from uveal melanoma and to determine the susceptibility of uveal melanoma cells to TRAIL-induced apoptosis.

Methods: Nine human uveal melanoma cell lines and three cell lines derived from uveal melanoma metastases were examined for TRAIL receptor expression by flow cytometry. In vitro apoptosis assays were performed to determine the relative susceptibility of uveal melanoma cells to TRAIL-induced apoptosis.

Splenic B cells act as antigen presenting cells for the induction of anterior chamber-associated immune deviation.

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

Methods: An in vitro model of the ACAID spleen was used to recapitulate the events that occur when antigen is introduced into the anterior chamber of the eye and culminates in the appearance of antigen-specific, CD8(+) suppressor cells.

Results: In vitro-generated suppressor cells mimicked those produced by anterior chamber injection of antigen, as shown by their antigen specificity, surface expression of CD8, and capacity to suppress DTH, which is mediated by previously immunized T cells.

CD25+, interleukin-10-producing CD4+ T cells are required for suppressor cell production and immune privilege in the anterior chamber of the eye.

An important factor in the establishment of ocular immune privilege is the dynamic down regulation of T helper 1 (Th1) immune responses that occurs in response to antigens delivered intraocularly; a phenomenon that has been termed anterior chamber-associated immune deviation (ACAID). ACAID is characterized by the generation of splenic regulatory cells that inhibit the expression of delayed-type hypersensitivity. Previous studies have shown that antigens introduced into the anterior chamber of the eye induce the generation of a CD4+ T-cell population that suppress the induction of Th1 immune responses and the appearance of a second population of CD8+ T regulatory cells that suppresses the expression of Th1 inflammatory responses (= efferent suppressor cells).

Reduction of liver metastasis of intraocular melanoma by interferon-beta gene transfer.

Purpose: This study determined whether adenovirus-mediated transfer of the murine interferon-beta (AdCMVIFN-beta) gene protects against liver metastases arising from intraocular melanomas in mice.

Methods: A replication-deficient adenovirus vector (AdCMVIFN-beta) was used for the in vivo transfer of the murine IFN-beta gene into intraocular melanoma-bearing mice. AdCMVIFN-beta was injected either intravenously or directly into the intraocular melanomas.

Are corneal cells susceptible to antibody-mediated killing in corneal allograft rejection?

Purpose: The precise role of antibodies in corneal transplantation is controversial. Clinical and experimental evidence both supports and refutes the contribution of donor-derived alloantibody in corneal allograft rejection. Accordingly, we prospectively evaluated the presence of donor-derived alloantibody in two high-risk donor-host combinations.

Preliminary findings in corneal allograft rejection in patients with keratoconus.

Purpose: Classically, corneal allograft rejection is thought to be a T(H)1-mediated phenomenon. However, T(H)2-mediated allograft rejection has been reported in other transplanted organ systems, including the heart and kidney. We previously reported a form of T(H)2-mediated corneal allograft rejection in a murine model with a T(H)2 immune bias.

Adaptive immune responses to Acanthamoeba cysts.

Acanthamoeba cysts are not eliminated from the corneas of human subjects or experimentally infected animals. The persistence of Acanthamoeba cysts in the cornea indicates that either the cysts escape immunological elimination or are not recognized by the host's immunological elements. The aim of this study was to determine the immunogenicity and antigenicity of the Acanthamoeba cyst.

Phenotypic analysis of oral tolerance to alloantigens: evidence that the indirect pathway of antigen presentation is involved.

Background: Oral administration of alloantigens induces down-regulation of Th1 immune responses and reduces the incidence of corneal graft rejection. 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.

Methods: Allogeneic dendritic cells (DC) were administered orally using a protocol that is known to reduce the incidence of corneal allograft rejection and prevent the generation of allospecific delayed-type hypersensitivity (DTH).