Functional Profile of Cytomegalovirus (CMV)-Specific CD8+ T Cells and Kinetics of NKG2C+ NK Cells Associated With the Resolution of CMV DNAemia in Allogeneic Stem Cell Transplant Recipients

Immune mechanisms involved in control of cytomegalovirus (CMV) infection in the allogeneic stem cell transplantation setting have not been fully disclosed. CMV pp65 and IE-1-specific CD8+ T cells expressing IFN-γ, TNF-α, and CD107a, alone or in combination, and NKG2C+ NK cells were prospectively enumerated during 13 episodes of CMV DNAemia. The expansion of monofunctional and polyfunctional CD8+ T cells was associated with CMV DNAemia clearance. The size and functional diversity of the expanding CD8+ T-cell population was greater in self-resolved episodes than in episodes treated with antivirals. These differences were related to the magnitude of expansion of cognate antigen IFN-γ CD4+ T cells. The resolution of CMV DNAemia was associated frequently with a marked expansion of both CD56dim/ CD16+ NK cells and NKG2C+ CD56bright/CD16― NK cells. The data lend support to the role of polyfunctional CD8+ T cells in controlling CMV replication in the allogeneic stem cell transplantation setting, and suggest that NKG2C+ NK cells may be involved critically in the resolution of CMV DNAemia episodes.