Clearance of HSV-2 from recurrent genital lesions correlates with infiltration of HSV-specific cytotoxic T lymphocytes

• Published in: The Journal of clinical investigation Vol. 101; no. 7; pp. 1500 - 1508
• Main Authors: Koelle, D M, Posavad, C M, Barnum, G R, Johnson, M L, Frank, J M, Corey, L
• Format: Journal Article
• Language: English
• Published: United States 01-04-1998
• Subjects: Adult; AIDS/HIV; CD8-Positive T-Lymphocytes - immunology; Female; Herpes Genitalis - immunology; Herpes Genitalis - virology; Herpes simplex virus 2; Herpesvirus 2, Human - immunology; Humans; Immunophenotyping; Lymphocyte Activation; Male; Recurrence; Skin - immunology; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 0021-9738
• DOI: 10.1172/JCI1758

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.