CD8+ dermal T cells from a sulphamethoxazole-induced bullous exanthem proliferate in response to drug-modified liver microsomes.
There is evidence that T lymphocytes play a critical role in the pathogenesis of drug-induced bullous exanthems. Sulphonamides are known to be among the most frequent aetiological agents in these severe drug-induced cutaneous hypersensitivity reactions. Several studies indicate that cytochrome P450-dependent metabolites of sulphonamides act as the nominal allergens. A 70-year-old woman with a severe blistering exanthem caused by cotrimoxazole (sulphamethoxazole and trimethoprim) was studied. We employed an in vitro approach to determine whether cytochrome P450-dependent enzymes activated drug-specific T lymphocytes from this patient. Immunohistochemical analysis of involved skin revealed a majority of epidermal CD8+ T lymphocytes, whereas the dermal infiltrate was composed of both CD4+ and CD8+ T cells. Dermal T lymphocytes isolated from lesional skin proliferated in response to sulphamethoxazole, but not to trimethoprim, in the presence of autologous mononuclear cells used as antigen-presenting cells. The antigen-specific response of sulphamethoxazole-specific T cells was significantly augmented in the presence of murine liver microsomes with P450-dependent catalytic activities. Our observations suggest that some cutaneous hypersensitivity reactions to sulphamethoxazole are due to drug-specific T lymphocytes. Cytochrome P450-dependent enzymes may play a critical role in the formation of the nominal antigen, which is recognized by antigen-specific T cells.
Hertl
M
M
Department of Dermatology, University of Cologne, Germany.
Jugert
F
F
Merk
H F
HF
D000368:Aged; D000818:Animals; D016827:CD8 Antigens / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000276:immunology*; D000939:Epitopes; D005076:Exanthema / Q000139:chemically induced*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000276:immunology; D008938:Mitosis; D013420:Sulfamethoxazole / Q000009:adverse effects*
D016827:CD8 Antigens; D000939:Epitopes; D003577:Cytochrome P-450 Enzyme System; D013420:Sulfamethoxazole