Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy

T cell receptor (TCR) gene therapy is a promising immunotherapy for cancer and infectious disease. But introducing exogenous TCR α and β chains into T cells may have unintended consequences. In this issue, Bendle et al. show that the transfer of TCR-transduced T cells into mice triggered a lethal pathology that resembles graft-versus-host disease and is caused by the pairing of endogenous and exogenous TCR chains resulting in autoreactive T cells (pages 520–521).