CD8(-CELLS FROM A SULFAMETHOXAZOLE-INDUCED BULLOUS EXANTHEM PROLIFERATE IN RESPONSE TO DRUG-MODIFIED LIVER-MICROSOMES() DERMAL T)

There is evidence that T lymphocytes play a critical role in the patho genesis of drug-induced bullous exanthems. Sulphonamides are known to be among the most frequent aetiological agents in these severe drug-in duced cutaneous hypersensitivity reactions. Several studies indicate t hat cytochrome P450-dependent metabolites of sulphonamides act as the nominal allergens. A 70-year-old woman with a severe blistering exanth em caused by cotrimoxazole (sulphamethoxazole and trimethoprim) was st udied. We employed an in vitro approach to determine whether cytochrom e P450-dependent enzymes activated drug-specific T lymphocytes from th is patient. Immunohistochemical analysis of involved skin revealed a m ajority of epidermal CD8(+) T lymphocytes, whereas the dermal infiltra te was composed of both CD4(+) and CD8(+) T cells. Dermal T lymphocyte s isolated from lesional skin proliferated in response to sulphamethox azole, but not to trimethoprim, in the presence of autologous mononucl ear cells used as antigen-presenting cells. The antigen-specific respo nse of sulphamethoxazole-specific T cells was significantly augmented in the presence of murine liver microsomes with P450-dependent catalyt ic activities, Our observations suggest that some cutaneous hypersensi tivity reactions to sulphamethoxazole are due to drug-specific T lymph ocytes. Cytochrome P450-dependent enzymes may play a critical role in the formation of the nominal antigen, which is recognized by antigen-s pecific T cells.