Massive clonal expansion of polycytotoxic skin and blood CD8 + T cells in patients with toxic epidermal necrolysis

Axel Patrice Villani , Aurore Rozieres , Benoît Bensaid , Klara Kristin Eriksson , Amandine Mosnier , Floriane Albert , Virginie Mutez , Océane Brassard , Tugba Baysal , Mathilde Tardieu , Omran Allatif (1) , Floriane Fusil , Thibault Andrieu , Denis Jullien , Valérie Dubois , Catherine Giannoli , Henri Gruffat , Marc Pallardy , François-Loïc Cosset (2) , Audrey Nosbaum , Osami Kanagawa , Janet L Maryanski , Daniel Yerly , Jean-François Nicolas , Marc Vocanson

1 BIBS - BioInformatique et BioStatistiques
2 EVIR - Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy

Toxic epidermal necrolysis (TEN) is a life-threatening cutaneous adverse drug reaction. To better understand why skin symptoms are so severe, we conducted a prospective immunophenotyping study on skin and blood. Mass cytometry results confirmed that effector memory polycytotoxic CD8 + 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.

Domaines: Sciences du Vivant [q-bio]

Axel Patrice Villani, Aurore Rozieres, Benoît Bensaid, Klara Kristin Eriksson, Amandine Mosnier, et al.. Massive clonal expansion of polycytotoxic skin and blood CD8 + T cells in patients with toxic epidermal necrolysis. Science Advances , 2021, 7 (12), pp.eabe0013. ⟨10.1126/sciadv.abe0013⟩. ⟨hal-03244260⟩