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

gamma delta 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 gamma delta 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 gamma delta 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 gamma delta TCRs during CMV reactivation. Given that the TCRs of CMV-activated gamma delta T cells are often cross-reactive to tumor cells, these findings pinpoint gamma delta T cells and their gamma delta TCRs as attractive multipurpose tools for antiviral and antitumor therapy.