Antigen-specific γδ T cells contribute to cytomegalovirus control after stem cell transplantation

γδ T cells support the immunological control of viral infections, in particular during cytomegalovirus (CMV) reactivation in immunocompromised patients after allogeneic hematopoietic stem cell transplantation. It is unclear how γδ T cells sense CMV-infection and whether this involves specific T cell receptor (TCR)-ligand interaction. Here we summarize recent findings that revealed an adaptive-like anti-CMV immune response of γδ T cells, characterized by acquisition of effector functions and long-lasting clonal expansion. We propose that rather CMV-induced self-antigen than viral antigens trigger γδ TCRs during CMV reactivation. Given that the TCRs of CMV-activated γδ T cells are often cross-reactive to tumor cells, these findings pinpoint γδ T cells and their γδ TCRs as attractive multipurpose tools for antiviral and antitumor therapy.