Increased numbers and functional activity of CD56⁺ T cells in healthy cytomegalovirus positive subjects.

Human T cells expressing CD56 are capable of tumour cell lysis following activation with interleukin-2 but their role in viral immunity has been less well studied. Proportions of CD56(+) T cells were found to be highly significantly increased in cytomegalovirus-seropositive (CMV(+) ) compared with seronegative (CMV(-) ) healthy subjects (9.1 ± 1.5% versus 3.7 ± 1.0%; P < 0.0001). Proportions of CD56(+) T cells expressing CD28, CD62L, CD127, CD161 and CCR7 were significantly lower in CMV(+) than CMV(-) subjects but those expressing CD4, CD8, CD45RO, CD57, CD58, CD94 and NKG2C were significantly increased (P < 0.05), some having the phenotype of T effector memory cells. Levels of pro-inflammatory cytokines and CD107a were significantly higher in CD56(+) T cells from CMV(+) than CMV(-) subjects following stimulation with CMV antigens. This also resulted in higher levels of proliferation in CD56(+) T cells from CMV(+) than CMV(-) subjects. Using Class I HLA pentamers, it was found that CD56(+) T cells from CMV(+) subjects contained similar proportions of antigen-specific CD8(+) T cells to CD56(-) T cells in donors of several different HLA types. These differences may reflect the expansion and enhanced functional activity of CMV-specific CD56(+) memory T cells. In view of the link between CD56 expression and T-cell cytotoxic function, this strongly implicates CD56(+) T cells as being an important component of the cytotoxic T-cell response to CMV in healthy carriers.