To investigate the cellular immune response to the drug lidocaine, we
generated T cell lines and clones from the peripheral blood of four pa
tients with proven allergy to lidocaine. The patients had contact derm
atitis after topical application of lidocaine, and local swelling or g
eneralized erythema exudativum multiforme after submucosal/subcutaneou
s injection of lidocaine. Two of three lidocaine-specific T cell lines
were oligoclonal and one even became monoclonal, while the simultaneo
usly analyzed immune response to tetanus toxoid was polyclonal. The li
docaine-specific T cell lines cross-reacted to mepivacaine, but not to
other local anesthetics (bupivacaine, procaine, oxybuprocaine, and te
tracaine). The majority of reactive T cells belonged to the CD4 cell l
ineage and were MHC class II restricted, but cloning also revealed som
e MHC class I-restricted CD8(+) clones. A total of 2 of 56 lidocaine-s
pecific T cell clones were CD4(-)CD8(-) and expressed TCR-gamma delta.
The majority of 13 analyzed CD4 clones produced a rather polarized cy
tokine pattern, with a dominance of Th2-like cytokines showing a high
IL-5 production. In addition, three CD4(+) and all CD8(+) (n = 7) clon
es secreted high IFN-gamma and low levels of IL-5/IL-4 (Th1-like). The
data illustrate that a drug that sensitizes via the skin elicits a he
terogeneous T cell response. The high IL-5 production and the particip
ation of specific CD4(+)CD8(+) and even gamma delta(+) T cells appear
to be distinguishing features of this hapten-specific immune response.