title: Increased cell-mediated immune responses in patients with recurrent herpes simplex virus type 2 meningitis.
abstract: The clinical picture of herpes simplex virus type 2 (HSV-2) infection includes genital blisters and less frequently meningitis, and some individuals suffer from recurrent episodes of these manifestations. We hypothesized that adaptive and/or innate immune functional deficiencies may be a major contributing factor in susceptibility to recurrent HSV-2 meningitis. Ten patients with recurrent HSV-2 meningitis were studied during clinical remission. For comparison, 10 patients with recurrent genital HSV infections as well as 21 HSV-seropositive and 19 HSV-seronegative healthy blood donors were included. HSV-specific T cell blasting and cytokine secretion were evaluated in whole blood cultures. HSV-2-induced NK cell gamma interferon production, dendritic cell Toll-like receptor (TLR) expression, and TLR agonist-induced alpha interferon secretion were analyzed. Patients with recurrent HSV-2 meningitis had elevated T cell blasting and Th1 and Th2 cytokine production in response to HSV antigens compared to those of patients with recurrent genital infections. A somewhat increased NK cell response, increased dendritic cell expression of TLR3 and -9, and increased TLR-induced alpha interferon responses were also noted. Contrary to our expectation, recurrent HSV-2 meningitis patients have increased HSV-specific adaptive and innate immune responses, raising the possibility of immune-mediated pathology in the development of recurrent HSV2 meningitis.
authors.affiliation: Infectious Diseases Unit, Department of Medicine, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Franzen-Röhl
authors.forename: Danika
authors.initials: D
authors.lastname: Schepis
authors.forename: Maria
authors.initials: M
authors.lastname: Lagrelius
authors.forename: Kristina
authors.initials: K
authors.lastname: Franck
authors.forename: Petra
authors.initials: P
authors.lastname: Jones
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Liljeqvist
authors.forename: Tomas
authors.initials: T
authors.lastname: Bergström
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Aurelius
authors.forename: Klas
authors.initials: K
authors.lastname: Kärre
authors.forename: Louise
authors.initials: L
authors.lastname: Berg
authors.forename: Hans
authors.initials: H
authors.lastname: Gaines
mesh_terms: D000328:Adult; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006561:Herpes Simplex / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008587:Meningitis, Viral / Q000276:immunology*; D008875:Middle Aged; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors