Long-term expansion of effector/memory Vδ2− γδ T cells is a specific blood signature of CMV infection

The ability of human gammadelta T cells to develop immunologic memory is still a matter of debate. We previously demonstrated the involvement of Vdelta2- gammadelta T lymphocytes in the response of immunosuppressed organ recipients to cytomegalovirus (CMV). Here, we demonstrate their ability to mount an adaptive immune response to CMV in immunocompetent subjects. Vdelta2- gammadelta T-cell peripheral blood numbers, repertoire restriction, and cytotoxicity against CMV-infected fibroblasts were markedly increased in CMV-seropositive, compared with CMV-seronegative, healthy persons. Whereas Vdelta2- gammadelta T cells were found as naive cells in CMV- patients, they virtually all exhibited the cytotoxic effector/memory phenotype in CMV+ patients, which is also observed in transplanted patients challenged with CMV. This long-term complete remodeling of the Vdelta2- gammadelta T-cell population by CMV predicts their ability to exhibit an adaptive anti-CMV immune response. Consistent with this, we observed that the secondary response to CMV was associated with a faster gammadelta T-cell expansion and a better resolution of infection than the primary response. In conclusion, the increased level of effector-memory Vdelta2- gammadelta T cells in the peripheral blood is a specific signature of an adaptive immune response to CMV infection of both immunocompetent and immunosuppressed patients.