Surface NKG2C Identifies Differentiated αβT-Cell Clones Expanded in Peripheral Blood

T cells that express CD56 in peripheral blood of healthy humans represent a heterogeneous and poorly studied subset. In this work, we analyzed this subset for NKG2C expression. In both CD56(+) and CD56(-) subsets most of the NKG2C(+) T cells had a phenotype of highly differentiated CD8(+) TEMRA cells. The CD56(+)NKG2C(+) T cells also expressed a number of NK cell receptors, such as NKG2D, CD16, KIR2DL2/DL3, and maturation marker CD57 more often than the CD56(-)NKG2C(+)CD3(+) cells. TCR beta-chain repertoire of the CD3(+)CD56(+)NKG2C(+) cell fraction was limited by the prevalence of one or several clonotypes which can be found within the most abundant clonotypes in total or CD8(+) T cell fraction TCR beta repertoire. Thus, NKG2C expression in highly differentiated CD56(+) T cells was associated with the most expanded alpha beta T cell clones. NKG2C(+) T cells produced almost no IFN-gamma in response to stimulation with HCMV pp65-derived peptides. This may be partially due to the high content of CD45RA(+)CD57(+) cells in the fraction. CD3(+)NKG2C(+) cells showed signs of activation, and the frequency of this T-cell subset in HCMV-positive individuals was positively correlated with the frequency of NKG2C(+) NK cells that may imply a coordinated in a certain extent development of the NKG2C(+) T and NK cell subsets under HCMV infection.

Automated summary

The study found that T cells expressing NKG2C in CD56(+) subset are highly differentiated and produce almost no IFN-gamma in response to HCMV stimulation, with their frequency positively correlated with NKG2C(+) NK cell frequency.