The role of CD4 and CD8 cytotoxic T lymphocytes in the formation of viral vesicles.
BACKGROUND
Herpetic vesicles caused by herpes simplex virus and varicella zoster virus, and hydroa vacciniforme (HV) are characterized by umbilicated vesicule formation.


OBJECTIVE
To understand the histogenesis of umbilicated vesicles in herpetic vesicles and HV, we demonstrated the presence of the virus-associated molecules in the lesions, and the pathogenic role of cytotoxic T-lymphocyte (CTL) immune responses.


METHODS
Phenotyping of infiltrating cells was carried out in biopsy specimens from herpes simplex, varicella, herpes zoster and HV, and compared with nonviral contact dermatitis. Viral antigens and Epstein-Barr virus-encoded small nuclear RNA (EBER) were detected by immunostaining and by in situ hybridization, respectively. Infiltrating CTLs expressing granzyme B and granulysin were determined by double immunostaining using confocal laser scanning microscopy.


RESULTS
In all herpetic vesicles, the corresponding viral antigens were observed in the cytopathic keratinocytes, and infiltration of lymphoid cells was present in the upper dermis and around the vessels. In all HV lesions studied, EBER+ T cells made up 5-10% of the dermal infiltrates and the dermal infiltrates contained almost no CD56 cells. CTLs expressing granzyme B and granulysin were present in both herpetic and HV lesions, in which they made up 10-30% of the total dermal infiltrates, whereas they comprised less than 5% of the infiltrates of biopsy specimens from nonviral contact dermatitis. Confocal laser microscopic examination demonstrated that both CD4+ and CD8+ T cells expressed granzyme B and granulysin.


CONCLUSIONS
CD4+ and/or CD8+ CTLs reactive to the virus-infected cells might be responsible for the histogenesis of herpetic and HV lesions characterized by umbilicated vesicles.
Morizane
S
S
Department of Dermatology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. gmd14058@cc.okayama-u.ac.jp
Suzuki
D
D
Tsuji
K
K
Oono
T
T
Iwatsuki
K
K
D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000956:Antigens, Viral / Q000032:analysis; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D053804:Granzymes; D006561:Herpes Simplex / Q000276:immunology / Q000473:pathology; D006562:Herpes Zoster / Q000276:immunology / Q000473:pathology; D006801:Humans; D006837:Hydroa Vacciniforme / Q000276:immunology / Q000473:pathology; D016130:Immunophenotyping; D017403:In Situ Hybridization / Q000379:methods; D018613:Microscopy, Confocal; D016601:RNA-Binding Proteins / Q000032:analysis; D012269:Ribosomal Proteins / Q000032:analysis; D012697:Serine Endopeptidases / Q000378:metabolism; D012872:Skin Diseases, Vesiculobullous / Q000276:immunology* / Q000473:pathology; D017193:Skin Diseases, Viral / Q000276:immunology* / Q000473:pathology
D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; C075005:GNLY protein, human; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; C067169:RPL22 protein, human; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases