PREDOMINANCE OF EPIDERMAL CD8-LYMPHOCYTES IN BULLOUS CUTANEOUS REACTIONS CAUSED BY BETA-LACTAM ANTIBIOTICS( T)

The phenotype and functional characteristics of skin-infiltrating lymp hocytes in beta-lactam antibiotic-induced vesiculobullous exanthems we re studied in vivo and in vitro. Immunohistochemical analysis demonstr ated that CD8+ T lymphocytes were the predominant epidermal T-cell sub set in these reactions. Epidermal T lymphocytes were isolated and expa nded 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 predom inance of epidermal CD8+ T lymphocytes found in situ. Three CD8+ epide rmal T-cell clones derived from cutaneous lesions proliferated in resp onse 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 clo nes produced significant amounts of interleukin-2, interferon-gamma, a nd granulocyte-macrophage colony-stimulating factor. Additionally, the T-cell clones displayed cytotoxicity against epidermal cells in lecti n-mediated cytotoxicity and against B-cell lines in T-cell receptor-tr iggered cytotoxicity. These data demonstrate the presence of epidermal drug-specific CD8+ T cells in bullous drug reactions. Because these C D8+ T cells have a cytotoxic potential, they may contribute to the nec rosis of keratinocytes associated with drug-induced blister formation.