M. Hertl et al., CD8(-CELLS FROM A SULFAMETHOXAZOLE-INDUCED BULLOUS EXANTHEM PROLIFERATE IN RESPONSE TO DRUG-MODIFIED LIVER-MICROSOMES() DERMAL T), British journal of dermatology, 132(2), 1995, pp. 215-220
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.