Highly Th2-skewed cytokine profile of beta-lactam-specific T cells from nonatopic subjects with adverse drug reactions

A positive lymphocyte transformation test to beta-lactams (beta-L) was foun d in 12 of 29 subjects with adverse drug reaction (ADR) to beta-L, irrespec tive of either the type of clinical manifestation or the presence of specif ic serum IgE, Short-term T cell lines specific for penicillin G, amoxicilli n, and ampicillin could be generated only from subjects with ADR (eight wit h positive and one with negative lymphocyte transformation test), while str eptokinase and Dermatophagoides pteronyssinus group 1 (Der p 1)-specific T cells were obtained from all these subjects, from 7 atopic Der p-sensitive donors without history of ADR and 17 healthy nonatopic donors. Streptokinas e-specific T cells from all subjects showed intracellular expression of IFN -gamma with poor or no IL-4, whereas Der p 1-specific T cells exhibited IFN -gamma but low or no IL-4 expression in nonatopics, and remarkable IL-4 exp ression in atopic donors. By contrast, all penicillin G-, ampicillin-, and amoxicillin-specific short-term T cell lines showed high intracellular expr ession of IL-4, IL-5, and IL-13, but poor or no expression of IFN-gamma, th us exhibiting a clear-cut Th2 profile. Accordingly, most penicillin G-speci fic T cell clones derived from two subjects with ADR released high concentr ations of IL-4 alone or IL-4 and IFN-gamma. These data suggest that cytokin es produced by Th2 cells play an important role in all beta-L-induced ADR, even when late clinical manifestations occur and an IgE-mediated mechanism is apparently indemonstrable.