Fragrances are worldwide a major cause of allergic contact dermatitis (ACD)
, a delayed-type hypersensitivity reaction mediated by T lymphocytes. We in
vestigated T cell responses to fragrances using peripheral blood mononuclea
r cells (PBMC) and T cells from skin lesions of fragrance-allergic patients
. The components of a fragrance mixture (eugenol, isoeugenol, geraniol, oak
moss, cr-amyl cinnamic aldehyde, cinnamic aldehyde, cinnamic alcohol, and
hydroxycitronellal) that is commonly used in the patch test were studied in
vitro in the lymphocyte transformation test (LTT). PBMC from fragrance-all
ergic patients (n = 32) showed significant stimulations to all eight fragra
nces. The calculated stimulation indices (SI) varied between 2.1 and 21.8,
The influence of metabolic enzymes on T cell stimulation was studied for tw
o fragrances. Interestingly, stimulation of eugenol and isoeugenol was incr
eased in the presence of antigen-modified human liver microsomes (CYP450) o
r recombinant CYP1A1 in five of seven cases. Furthermore, we established 18
T cell clones (TCC) from a skin lesion reacting specifically to eugenol. F
AGS analysis revealed that the majority (n = 15, 83%) of TCC were CD3(+), C
D4(+), and HLA-DR+. Seventeen percent (n = 3) of the clones were CD8(+). TC
C (n = 4) released significant amounts of IL-2 and IFN-gamma but no IL-4 an
d IL-5. In addition, CD4(+) TCC (n = 3) showed antigen-induced cytotoxic ac
tivities against autologous B cells. In summary, we demonstrated for the fi
rst time that fragrance-specific CD4(+) and CD8(+) T lymphocytes are presen
t in fragrance-allergic individuals. In addition, our results suggest that
CYPs can be involved in the formation of the nominative antigen. (C) 2001 A
cademic Press.