T cell reactivity to penicillin: phenotypic analysis of in vitro activated cell subsets

Patients with penicillin allergy demonstrate a T cell proliferative response after in vitro stimulation with penicillin G (Pen G) and other beta-lactam antibiotics. To understand better penicillin-allergic reactions, T cell subset stimulation with Pen G was studied and compared with other soluble (tetanus toxoid and purified protein derivative [PPD]) and membrane-bound viral (influenza A and Epstein-Barr viruses) antigens. A double fluorescence method for flow cytometry was used to evaluate the activated cells simultaneously by pyronin Y staining of RNA and by indirect immunofluorescence of cell surface T4, T8, or Leu 8 antigens. The antigens used stimulated mainly the T4+ subset (greater than 90%), whereas the number of activated T8 cells was slightly increased only in Pen G- and influenza A-triggered cultures (5% to 15%). Leu 8 antigen was used to analyze more precisely the activated T4+ cells. Pen G and influenza A and Epstein-Barr viruses stimulated both T4+, Leu 8+ (greater than 50% of activated cells, inducers for suppressor cells), and T4+, Leu 8- (helpers for B cells) subsets, whereas PPD activated mainly T4+, Leu 8- subpopulations. These results indicate that penicillin-allergic patients with skin symptoms demonstrate a T cell subset stimulation that resembles more the reaction versus viral antigens (membrane incorporated) than to soluble antigens like PPD. These results suggest that Pen G is presented to T cells like viral proteins and might thus cause allergic reactions resembling skin symptoms observed in viral diseases.