Patients with gastrointestinal irritability after TGN1412-induced cytokine 2 storm displayed selective expansion of gut-homing αβ and γδ T-cells

Abstract

Following infusion of the anti-CD28 superagonist monoclonal antibody TGN1412, three of six previously healthy, young male recipients developed gastrointestinal irritability associated with increased expression of ‘gut-homing’ integrin β7 on peripheral blood αβT-cells. This subset of patients with intestinal symptoms also displayed a striking and persistent expansion of putative Vδ2+ 7 γδT-cells in the circulation which declined over a two-year period following drug infusion, concordant with subsiding gut symptoms. These data demonstrate that TGN1412-induced gastrointestinal symptoms were associated with dysregulation of the ‘gut-homing’ pool of blood αβ and γδT11 cells, induced directly by the antibody and/or arising from the subsequent cytokine storm.