Adoptive γδ T cell therapy controls cytomegalovirus infection in preclinical transplantation models

γδ T cells show promise for anti-tumoral therapies but have yet to be evaluated to treat infectious diseases. In this preclinical study, we assess a Vδ1 + γδ T cell-based adoptive cell therapy, named Delta One T cells, to treat cytomegalovirus (CMV) infection in high-risk transplant recipients. Even when expanded from CMV-naïve healthy donors, Delta One T cells efficiently control CMV dissemination in vitro. CMV recognition is independent of the γδTCR but requires LFA-1 co-stimulation. In an in vivo model, adoptive transfer of mouse γδ T cells recapitulating Delta One T cell features protects mice against lethal murine CMV infection. Importantly, CMV-reactive Delta One T cells can be successfully generated from kidney transplant recipients undergoing refractory CMV infections and maintain their functionality in the presence of immunosuppressive drugs. These findings broaden the scope of γδ T cell therapies to infectious diseases and uncover a universal adoptive T cell therapy to treat refractory CMV infections.