IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination.

Previously we reported that a recombinant HSV-1 expressing murine IL-2 (HSV-IL-2) causes CNS demyelination in different strains of mice and in a T cell-dependent manner. Since T17 cells have been implicated in CNS pathology, in the present study, we looked into the effects of IL-17A and three of its receptors on HSV-IL-2-induced CNS demyelination. IL-17A mice did not develop CNS demyelination, while IL-17RA, IL-17RC, IL-17RD and IL-17RARC mice developed CNS demyelination.

CCR6-Positive γδ T Cells Provide Protection Against Intracorneal HSV-1 Infection.

Purpose: γδ T cells offer an important early immune defense against many different pathogens, both bacterial and viral. Herein, we examined the capacity of γδ T cell subsets to provide protection in the cornea against herpes simplex virus-1 (HSV-1).

Methods: C57Bl/6 (wild-type [WT]), γδ T-cell deficient (TCRδ-/-) and CCR6-deficient (CCR6-/-) mice were infected intracorneally with HSV-1.

Expression, Inducers and Cellular Sources of the Chemokine MIG (CXCL 9), During Primary Herpes Simplex Virus Type-1 Infection of the Cornea.

Purpose: To investigate the production of monokine induced by gamma-interferon (MIG) during a primary Herpes simplex virus type 1 (HSV-1) infection of the cornea. We hypothesize that multiple CXCR3 ligands are involved in T cell recruitment during HSV-1 corneal infection and that neutrophils have the potential to contribute to their production.

Materials And Methods: Levels of MIG were evaluated in an in vivo murine model of HSV-1 corneal infection by quantitative ELISA.

IL-17 receptor signaling influences virus-induced corneal inflammation.

IL-17 has been associated with selected inflammatory and autoimmune diseases. We characterized the expression of this proinflammatory cytokine following HSV-1 corneal infection and investigated whether IL-17R signaling modulated the host response to the viral pathogen at early time-points postinfection. IL-17 was elevated in the murine cornea 24 h after high-dose virus infection and subsequently persisted at low levels during the first week.

Human corneal epithelial cells synthesize ELR(-)alpha-chemokines in response to proinflammatory mediators.

The purpose of this study was to characterize the synthesis of alpha-chemokines IP-10, MIG, and I-TAC by human corneal epithelial cells (HCE) following exposure to proinflammatory mediators. Supernatants were collected from HCE cultures stimulated with individual or combinations of TNF-alpha, IL-1alpha, and IFN-gamma, and assayed for alpha-chemokines by ELISA. RT-PCR was used to detect IFN-gamma receptor mRNA.

Synthesis of alpha-chemokines IP-10, I-TAC, and MIG are differentially regulated in human corneal keratocytes.

Purpose: Chemokines responsible for recruiting lymphocytes such as activated T cells into the cornea have not been clearly defined. IP-10, I-TAC, and MIG are chemoattractants for these lymphocytes. The goal of this study was to determine whether human corneal keratocyte (HCKs) in culture synthesize these chemokines in response to proinflammatory mediators.

CXCR3, IP-10, and Mig are required for CD4+ T cell recruitment during the DTH response to HSV-1 yet are independent of the mechanism for viral clearance.

Sensitized CD4+ T cells play an essential role in delayed type hypersensitivity (DTH) elicited by HSV-1 antigen. As activated CD4+ T cells express CXCR3, we investigated whether this chemokine receptor was involved in their recruitment. Antibody blockade of CXCR3 suppressed DTH, whereas ear pinna swelling was not impaired in mice lacking the gene for CCR5, another frequently expressed chemokine receptor.

Activation of cytokines and NF-kappa B in corneal epithelial cells infected by respiratory syncytial virus: potential relevance in ocular inflammation and respiratory infection.

Background: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection, claiming millions of lives annually. The virus infects various cells of the respiratory tract as well as resident inflammatory cells such as macrophages. Infection activates a variety of cellular factors such as cytokines and the pro-inflammatory transcription factor, NF-kappa B, all of which are important players in the respiratory disease.

A role for NF-kappa B binding motifs in the differential induction of chemokine gene expression in human corneal epithelial cells.

Purpose: The interleukin (IL)-8 promoter possesses a NF-kappa B-binding site with affinity to p50p65 and p65p65 complexes while the monocyte chemoattractant protein (MCP)-1 promoter's NF-kappa B-binding site has exclusive affinity to p50p65 heterodimers. The purpose of this study was to determine whether the two NF-kappa B sites play a role in the capacity of tumor necrosis factor (TNF)-alpha-stimulated human corneal epithelial cells (HCECs) to produce nanogram amounts of IL-8 in the absence of MCP-1 synthesis.

Methods: IL-8 and MCP-1 promoters were cloned into luciferase reporter vectors.

Differential regulation of ENA-78 and GCP-2 gene expression in human corneal keratocytes and epithelial cells.

Purpose: To determine whether interleukin (IL)-1alpha- and tumor necrosis factor (TNF)-alpha-stimulated human corneal epithelial cells (HCECs) and human corneal keratocytes (HCKs) produce the alpha-chemokines epithelial cell-derived neutrophil attractant (ENA)-78 and granulocyte chemotactic protein (GCP)-2.

Methods: Cultures of HCECs and HCKs were stimulated with either human recombinant IL-1alpha or TNF-alpha. At selected times after stimulation, culture supernatants were harvested and assayed for ENA-78 and GCP-2 by enzyme-linked immunosorbent assay.

Involvement of CD40-CD40L signaling in postischemic lung injury.

Our studies show that ischemia-reperfusion (I/R) in the isolated rat lung causes retention of lymphocytes, which is associated with increased microvascular permeability, as determined by quantitative measurement of the microvascular filtration coefficient (K(f,c)). Immunoneutralization of either CD40 or CD40L, cell surface proteins important in lymphocyte-endothelial cell proinflammatory events, results in significantly lower postischemic K(f,c) values. Antagonism of CD40-CD40L signaling also results in attenuation of I/R-elicited macrophage inflammatory protein-2 production.

Role for macrophage inflammatory protein 2 (MIP-2), MIP-1alpha, and interleukin-1alpha in the delayed-type hypersensitivity response to viral antigen.

BALB/c mice sensitized to herpes simplex virus type 1 (HSV-1) develop a vigorous delayed-type hypersensitivity (DTH) response upon intradermal virus antigen challenge. Although CD4(+) T cells are a key mediator of this response, neutrophils are the most abundant cells at the antigen challenge site both initially and at the peak of the reaction. We investigated what role, if any, neutrophils play in the DTH to a viral antigen.

Linkage of IL-6 with neutrophil chemoattractant expression in virus-induced ocular inflammation.

Purpose: Herpes simplex virus (HSV)-1 infection of the murine cornea is known to stimulate a vigorous interleukin (IL)-6 response, but whether this pleiotropic cytokine is an essential participant in corneal inflammation is unclear. This study was designed to compare the early inflammatory response in IL-6 gene-deficient mice to that in wild-type hosts.

Methods: Gene knockout and wild-type mice (C57BL/6 background) were infected intracorneally with HSV-1 (strain RE) and observed through clinical examination and immunohistochemistry for the development of corneal opacity.