Direct T-cell stimulations by drugs--bypassing the innate immune system.
Some drug induced immune mediated side effects appear rapidly (6-<48hrs) and are hard to reconcile with the generation of a new immune response to the drug. By extending the previously presented p-i concept (pharmacological interaction with immune receptors), I propose that drugs might stimulate memory T-cells via their T-cell receptors, which happen to react not only with a peptide antigen, but also with a (chemically inert) drug. In this model, the generation of a new, drug specific immune response is actually bypassed: the innate immune system must not be stimulated, as no naive T-cells are stimulated. Only previously activated memory T-cells are re-activated, as they have a lower threshold of reactivity to a T-cell receptor transmitted signal, whereby certain cofactors like an ongoing immune response to a virus might facilitate reactivity to the drug. This concept has major implications for preclinical testing of the allergenic potential of a drug, which normally is measured by the ability of the drug to cause a new immune response.
Pichler
Werner J
WJ
Division of Allergology, Clinic for Rheumatology and Clinical Immunology/Allergology, Inselspital, University of Berne, CH-3010 Berne, Switzerland. werner.pichler@insel.ch
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D004342:Drug Hypersensitivity / Q000503:physiopathology; D006241:Haptens / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D006241:Haptens