M. Hertl et al., PREDOMINANCE OF EPIDERMAL CD8-LYMPHOCYTES IN BULLOUS CUTANEOUS REACTIONS CAUSED BY BETA-LACTAM ANTIBIOTICS( T), Journal of investigative dermatology, 101(6), 1993, pp. 794-799
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.