Massive clonal expansion of polycytotoxic skin and blood CD8 <sup>+</sup> T cells in patients with toxic epidermal necrolysis
A. Villani, Aurore Rozières, Benoît Bensaïd, Klara Eriksson, A. Mosnier, Floriane Albert, Virginie Mutez, Océane Brassard, Tugba Baysal, M. Tardieu, Omran Allatif, Floriane Fusil, Thibault Andrieu, D. Jullien, Valérie Dubois, C. Giannoli, Henri Gruffat, Marc Pallardy, François‐Loïc Cosset, Audrey Nosbaum, Osami Kanagawa, Janet L. Maryanski, Daniel Yerly, Jean‐François Nicolas, Marc Vocanson
Abstract
T cells (CTLs) are the main leucocytes in TEN blisters at the acute phase. Deep T cell receptor (TCR) repertoire sequencing identified massive expansion of unique CDR3 clonotypes in blister cells. The same clones were highly expanded in patient's blood, and the degree of their expansion showed significant correlation with disease severity. By transducing α and β chains of the expanded clonotypes into a TCR-defective cell line, we confirmed that those cells were drug specific. Collectively, these results suggest that the relative clonal expansion and phenotype of skin-recruited CTLs condition the clinical presentation of cutaneous adverse drug reactions.