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

McCarthy, Neil E.; Stagg, Andrew J.; Price, Claire L.; Mann, Elizabeth R.; Gellatly, Nichola L.; Al-Hassi, Hafid O.; Knight, Stella C.; Panoskaltsis, Nicki

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(+) γδT cells in the circulation which declined over a 2-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 γδT cells, induced directly by the antibody and/or arising from the subsequent cytokine storm. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-020-02723-4) contains supplementary material, which is available to authorized users.