Clearance of HSV-2 from recurrent genital lesions correlates with infiltration of HSV-specific cytotoxic T lymphocytes.
The mechanisms involved in host clearance of symptomatic mucocutaneous herpes simplex virus (HSV) infection are unclear. We studied the functional properties of bulk cultures of skin-infiltrating lymphocytes from normal skin and serial biopsies of recurrent genital HSV-2 lesions, and compared HSV-specific and NK responses with viral clearance. HSV-specific CD4+ or CD8+ T cells were rarely detected in lymphocytes cultured from normal skin. The total lymphocyte count and HSV-specific and NK-like effector cell activities were markedly higher in cultures derived from lesional skin. HSV-specific CD4+ proliferative responses and NK-like cytotoxic responses were present at all stages of herpetic lesions, including biopsies early in the disease course. In contrast, cytotoxic T lymphocyte activity was generally low among cells derived from early culture-positive lesions, and increased during lesion evolution. Viral clearance from the lesion site was associated with a high level of local cytolytic activity towards HSV-infected cells. The phenotypes of cells with HSV-specific cytotoxic responses varied between patients, having CD4+ and CD8+ components. Immunotherapeutic approaches to HSV should be directed at improving in vivo cytolytic activity to HSV.
Koelle
D M
DM
Department of Medicine, University of Washington, Seattle, Washington 98195, USA. viralimm@u.washington.edu
Posavad
C M
CM
Barnum
G R
GR
Johnson
M L
ML
Frank
J M
JM
Corey
L
L
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008297:Male; D012008:Recurrence; D012867:Skin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*