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Herpes simplex virus-specific immune responses in subjects with frequent and infrequent orofacial recrudescences


Professor Mary Norval. E-mail:


Background  Following the primary infection of the orofacial region with herpes simplex virus (HSV) type 1, the virus remains latent in the ganglia for the lifetime of the host but can reactivate at intervals and cause recrudescent lesions. The frequency of these episodes varies considerably from one individual to another.

Objectives  To compare immune responses in two groups of subjects: those with frequent orofacial lesions, defined as 10 or more per year (n = 12), and those with infrequent lesions, defined as three or fewer per year (n = 20).

Methods  Plasma and peripheral blood mononuclear cells were collected from each individual for the series of immunological tests listed in the following results section.

Results  Although IgG titres specific for HSV, measured by enzyme-linked immunosorbent assay (ELISA), were not different between the two groups, there was a significantly higher HSV-specific IgE titre in the frequent group. The percentages of CD3-, CD4- and CD8-positive cells in peripheral blood, assessed by flow cytometry, and the in vitro lymphoproliferative response to the non-specific mitogen concanavalin A, did not differ between the two groups. T-cell responses to HSV were assessed by in vitro lymphoproliferation with tritiated thymidine incorporation and subsequent calculation of the stimulation index; cytokine production [interferon (IFN)-γ and interleukin (IL)-10] into the culture supernatant as a result of the stimulation was measured by ELISAs. The mean ± SEM stimulation index was 4·1 ± 0·2 in the subjects with frequent lesions and 11·8 ± 3·1 in the subjects with infrequent lesions, a difference that was significant. The mean IL-10 concentrations found in the subjects with frequent and infrequent lesions were 154 and 110 pg mL−1, respectively, a difference that did not reach significance. However, the IFN-γ production was significantly lower in the subjects with frequent lesions compared with those with infrequent lesions: mean 835 and 1679 pg mL−1, respectively.

Conclusions  Thus, from the HSV-specific T-cell proliferation, IFN-γ production and IgE results, patients who experience frequent recrudescences may tend towards the production of T-helper 2 cytokines in response to the virus, which may lead, in turn, to less effective control of viral replication in the periphery following reactivation from latency.