Predominance of epidermal CD8+ T lymphocytes in bullous cutaneous reactions caused by beta-lactam antibiotics.
The phenotype and functional characteristics of skin-infiltrating lymphocytes in beta-lactam antibiotic-induced vesiculobullous exanthemas were studied in vivo and in vitro. Immunohistochemical analysis demonstrated that CD8+ T lymphocytes were the predominant epidermal T-cell subset in these reactions. Epidermal T lymphocytes were isolated and expanded for in vitro studies. Fluorescence-activated cell sorter analysis showed the majority of epidermal T cells to be CD3+, T-cell receptor alpha/beta+, CD4-, CD8+, and HLA-DR+, which correlated with the predominance of epidermal CD8+ T lymphocytes found in situ. Three CD8+ epidermal T-cell clones derived from cutaneous lesions proliferated in response to penicillin-pulsed autologous antigen-presenting cells but not allogeneic antigen-presenting cells, indicating that those clones were antigen and major histocompatibility complex specific. All T-cell clones produced significant amounts of interleukin-2, interferon-gamma, and granulocyte-macrophage colony-stimulating factor. Additionally, the T-cell clones displayed cytotoxicity against epidermal cells in lectin-mediated cytotoxicity and against B-cell lines in T-cell receptor-triggered cytotoxicity. These data demonstrate the presence of epidermal drug-specific CD8+ T cells in bullous drug reactions. Because these CD8+ T cells have a cytotoxic potential, they may contribute to the necrosis of keratinocytes associated with drug-induced blister formation.
Hertl
M
M
Department of Dermatology, University of Cologne, Germany.
Bohlen
H
H
Jugert
F
F
Boecker
C
C
Knaup
R
R
Merk
H F
HF
D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000166:cytology; D000954:Antigens, Surface / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis*; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007150:Immunohistochemistry; D012867:Skin / Q000166:cytology*; D012872:Skin Diseases, Vesiculobullous / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D016827:CD8 Antigens; D016207:Cytokines; D047090:beta-Lactams