Antigen presentation and systematic immune responses to herpes simplex virus in patients with recrudescent facial herpetic infections

Vestey, James Patrick (1990) Antigen presentation and systematic immune responses to herpes simplex virus in patients with recrudescent facial herpetic infections. University of Southampton, Doctoral Thesis.

Abstract

There is evidence that cell mediated immunity is important in the recovery from herpes simplex virus (HSV) infections but antibodies may help prevent spread of the virus to the nervous system. In this study the relationship between lymphoproliferative and antibody responses to HSV was examined during and after recrudescent HSV infection in healthy volunteers with facial HSV infection and control subjects with no history of herpetic infection. All patients had circulating antibodies to HSV and HSV-specific in vitro lymphoproliferation; controls were negative for both tests. The lymphoproliferative response to HSV was shown to fluctuate: during recrudescence it was low, rose to a peak 5-8 weeks later, and declined over several weeks to a positive background level. Lymphoproliferation with concanavalin A (con A) and circulating anti-HSV antibody titres were high throughout and peripheral blood mononuclear cell subsets remained normal. Evidence was obtained that reduced lymphoproliferative responses to HSV during recrudescence were due to HSV-specific suppressor T cell function rather than lack of responsive T cells. This may cause depression of normal cell mediated immune responses to HSV during asymptomatic recurrences, allowing recrudescent lesions to develop. Three patients with severe eczema herpeticum had absent cell mediated immunity to HSV for many months after recovery from the infection despite normal responses to con A, circulating anti-HSV antibody levels and peripheral blood mononuclear cell subsets. Experimental results suggested that impaired cell mediated immunity to HSV, which might have contributed to the severity of their infection, could be due to suppressor function of CD8⁺ cells. Activation of helper T cells, which is necessary for effective local cell mediated immune responses to epidermal HSV infection, required presentation of HSV antigen on the surface of antigen presenting cells in the context of Major Histocompatibility Complex (MHC) class II antigen. Epidermal cells, particularly Langerhans cells have antigen presenting function for many antigens. The antigen presenting function of epidermal cells for HSV was investigated in patients with recrudescent HSV infections. Epidermal cell suspensions, prepared from suction blister roofs, and glass-adherent peripheral blood mononuclear cells both presented HSV to immune T cells but epidermal cells were more efficient antigen presenting cells than adherent cells on a per cell basis. Antigen presentation was carried out by DP+ DQ+ DR+ CD1a+ epidermal cells, shown to be Langerhans cells by electron microscopy. Preincubation of epidermal or blood adherent cells with monoclonal antibodies to MHC class II DP, DQ or DR antigens blocked lymphoproliferative responses to HSV. Depletion of DP+ cells from adherent cells also depleted DR+ and DQ+ cells and the antigen presenting cell function of adherent cells was concentrated in cells expressing DP, DQ and DR Ag.

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