γδ T Cell-Mediated immunity to Cytomegalovirus infection

gamma delta T lymphocytes are unconventional immune cells, which have both innate- and adaptive-like features allowing them to respond to a wide spectrum of pathogens. For many years, we and others have reported on the role of these cells in the immune response to human cytomegalovirus in transplant patients, pregnant women, neonates, immunodeficient children, and healthy people. Indeed, and as described for CD8(+) T cells, CMV infection leaves a specific imprint on the gamma delta T cell compartment: (i) driving a long-lasting expansion of oligoclonal gamma delta T cells in the blood of seropositive individuals, (ii) inducing their differentiation into effector/memory cells expressing a T-EMRA phenotype, and (iii) enhancing their antiviral effector functions (i.e., cytotoxicity and IFN gamma production). Recently, two studies using murine CMV (MCMV) have corroborated and extended these observations. In particular, they have illustrated the ability of adoptively transferred MCMV-induced gamma delta T cells to protect immune-deficient mice against virus-induced death. In vivo, expansion of gamma delta T cells is associated with the clearance of CMV infection as well as with reduced cancer occurrence or leukemia relapse risk in kidney transplant patients and allogeneic stem cell recipients, respectively. Taken together, all these studies show that gamma delta T cells are important immune effectors against CMV and cancer, which are life-threatening diseases affecting transplant recipients. The ability of CMV-induced gamma delta T cells to act independently of other immune cells opens the door to the development of novel cellular immunotherapies that could be particularly beneficial for immunocompromised transplant recipients.