BACKGROUND: Delayed allergic skin reactions to drugs are common iatrogenic diseases mediated by activation of specific T cells in the skin. METHODS: To better understand the role of T cells in these diseases, we developed a mouse model of drug allergy induced by skin sensitization to amoxicillin (amox), a penicillin antibiotic frequently involved in delayed drug allergy. RESULTS: Whereas wild-type mice could not be sensitized to amox, CD4+ T-cell-deficient mice developed an amox-specific allergic skin response, mediated by IFN-gamma-producing CD8+ T cells. Amox-specific CD8+ T cells, induced in lymphoid organs at a high frequency during sensitization, were recruited in the skin upon challenge. CD8+ T cells were effectors of the allergic skin reaction to amox as in vivo treatment with depleting anti-CD8 mAbs abrogated the skin inflammatory reaction and as purified CD8+ T cells could adoptively transfer the allergic response to naive recipients. CONCLUSION: CD8+ T cells mediate penicillin skin allergy.
BACKGROUND: Delayed allergic skin reactions to drugs are common iatrogenic diseases mediated by activation of specific T cells in the skin. METHODS: To better understand the role of T cells in these diseases, we developed a mouse model of drug allergy induced by skin sensitization to amoxicillin (amox), a penicillin antibiotic frequently involved in delayed drug allergy. RESULTS: Whereas wild-type mice could not be sensitized to amox, CD4+ T-cell-deficient mice developed an amox-specific allergic skin response, mediated by IFN-gamma-producing CD8+ T cells. Amox-specific CD8+ T cells, induced in lymphoid organs at a high frequency during sensitization, were recruited in the skin upon challenge. CD8+ T cells were effectors of the allergic skin reaction to amox as in vivo treatment with depleting anti-CD8 mAbs abrogated the skin inflammatory reaction and as purified CD8+ T cells could adoptively transfer the allergic response to naive recipients. CONCLUSION: CD8+ T cells mediate penicillinskin allergy.
Authors: Pamela L Scheinman; Marc Vocanson; Jacob P Thyssen; Jeanne Duus Johansen; Rosemary L Nixon; Kate Dear; Nina C Botto; Johanna Morot; Ari M Goldminz Journal: Nat Rev Dis Primers Date: 2021-05-27 Impact factor: 52.329