How Herpes Simplex Virus Type 1 Rescinds Corneal Privilege

Abstract

Properties of the cornea such as a lack of blood and lymphatic vessels, a lack of professional antigen-presenting cells, and exposure to immunosuppressive factors in the aqueous humor contribute to a relative state of immune privilege. Ironically, corneal damage and the accompanying visual morbidity following herpes simplex virus type 1 (HSV-1) infection does not results from uncontrolled viral replication, but from an immunoinflammatory process referred to as herpes stromal keratitis (HSK). This review highlights changes in the immune-privileged status of the cornea following HSV-1 infection that contribute to HSK.

αβ TCR+T Cells, but Not B Cells, Promote Autoimmune Keratitis in B10 Mice Lacking γδ T Cells

“…Mice with herpes stromal keratitis, an infectious disease that eventually progresses to autoimmune keratitis after the virus (HSV) has been cleared (reviewed in Ref. 4), have been shown to be particularly susceptible to progression to HSV infection of the brain if they lack ␥␦ T cells, 5 consistent with the idea that ␥␦ T cells normally downregulate immune responses that are evoked in the cornea and thus prevent inflammatory damage that leads to this complication. Increases in ␥␦ T cells during autoimmune disorders of the human eye have also been noted, including Behçet's disease 6 and ocular cicatricial pemphigoid, 7,8 as well as in chronic corneal graft rejection, 8 which suggests that ␥␦ T cells play a similar regulatory role in the human eye.…”

Acyclovir‐Resistant Corneal HSV‐1 Isolates from Patients with Herpetic Keratitis

“…The present study is the first to report an unprecedented relatively high (6.4%) prevalence of ACV R corneal HSV-1 isolates in immunocompetent patients with HK. We hypothesize that this high prevalence could be due to the unique immuneprivileged site of the cornea, which differs from other HSV-1 infection sites [15]. At the Rotterdam Eye Hospital, where all patients with HSV-1 have been treated, prophylactic treatment with ACV has greatly increased since 1994; because all ACV R isolates identified in the present study came from patients who presented after 1994, we hypothesize that the increase in ACV prescriptions may have influenced the emergence of ACV R corneal HSV-1 at this hospital.…”

Current Concepts in the Management of Herpes Simplex Anterior Segment Eye Disease

“…The role of retained viral antigen as a stimulus for chronic inflammation (focal, multifocal or diffuse) and T cell-mediated autoimmune responses in murine models have been studied but the role of live virus in the pathogenesis of immune stromal keratitis has not been elucidated fully [33]. It is hypothesized that stromal inflammation is driven by either HSV-1-specific CD4þ T cells stimulated directly by viral antigens, bystander cytokine activation of CD4þ T cells, auto-antigens unmasked and mimicked by HSV-1 corneal infection or a combination of these processes [34].…”