Characterization of secreted and intracellular forms of a truncated hepatitis C virus E2 protein expressed by a recombinant herpes simplex virus.

A replication-defective herpes simplex virus type 1 (HSV-1) recombinant lacking the glycoprotein H (gH)-encoding gene and expressing a truncated form of the hepatitis C (HCV) E2 glycoprotein (E2-661) was constructed and characterized. We show here that cells infected with the HSV/HCV recombinant virus efficiently express the HCV E2-661 protein. Most importantly, cellular and secreted E2-661 protein were both readily detected by the E2-conformational mAb H53 and despite the high expression levels, only limited amounts of misfolded aggregates were detected in either the cellular or secreted fractions.

Modulating phenotype and cytokine production of leucocytic retinal infiltrate in experimental autoimmune uveoretinitis following intranasal tolerance induction with retinal antigens.

Background/aim: Nasal administration of retinal antigens induces systemic tolerance which results in suppression of experimental autoimmune uveoretinitis (EAU) when subsequently exposed to antigen. The aim was to establish if tolerance induction alters retinal infiltrating leucocyte phenotype and cytokine profile in tolerised animals when there is significantly reduced tissue destruction despite immunisation with retinal antigen.

Methods: Female Lewis rats were tolerised by intranasal administration with retinal extract (RE) before immunisation with RE to induce EAU.

Intranasal administration of retinal antigens induces transient T cell activation and apoptosis within drainage lymph nodes but not spleen.

Mechanisms of mucosal tolerance induction, including anergy/deletion and active suppression are frequently described as mutually exclusive; dependent upon nature, dose and route of antigen administration. We have previously described induction of low-dose tolerance with administration of retinal autoantigens via the nasorespiratory tract which is antigen-specific, suppresses both cell mediated immunity and ultimately tissue destruction in experimental autoimmune uveoretinitis (EAU) and is mediated by splenic-derived regulatory cells. The present data further shows that splenocytes or fractionated splenic T cells, which secrete IL-4 and IL-10 when stimulated with retinal antigen in vitro, and not regional drainage lymph node cells transfer tolerance to naïve animals.

Effects of mycophenolate mofetil on nasal mucosal tolerance induction.

Purpose: The authors investigated mucosal tolerance therapy as a treatment for autoimmune conditions, including uveitis. Although nasal antigen administration was unable to suppress the disease when given to primed animals, previous studies of experimental autoimmune uveoretinitis (EAU) have shown that nasal antigen administration can maintain disease suppression when combined with oral cyclosporin A. This study aimed to determine whether mucosal tolerance can be induced when EAU is suppressed with mycophenolate Mofetil (MM) and whether tolerance can be maintained when immunosuppression with MM is stopped.

Phenotypic analysis of retinal leukocyte infiltration during combined cyclosporin A and nasal antigen administration of retinal antigens: delay and inhibition of macrophage and granulocyte infiltration.

Nasal antigen administration successfully suppresses a model of organ-specific autoimmune disease, experimental autoimmune uveoretinitis (EAU), when administered prior to immunisation. We have previously shown that nasal antigen therapy for active disease or in primed, sensitised animals does not reliably or consistently suppress histological disease. However, when nasal antigen administration is combined with cyclosporin A (CsA) therapy, rod outer segment destruction (target organ) is reduced despite the presence of clinical and histological leukocytic infiltration of the eye.