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

Abstract

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 β-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 TCRβ repertoire. Thus, NKG2C expression in highly differentiated CD56+ T cells was associated with the most expanded αβ T cell clones. NKG2C+ T cells produced almost no IFN-γ 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.

Alterations in the CD56− and CD56+ T Cell Subsets during COVID-19

“…It was shown earlier that surface NKG2C marks the most differentiated cells in both CD56 + and CD56 − T cell subsets [6]. In this study, we did not detect any statistically significant difference in the proportion of NKG2C + cells among either total T cells or CD56 − and CD56 + T cell subsets between healthy donors, COVID-19 patients, and convalescents (Figure S4).…”

“…Activating NK cell receptors NKG2D and CD16 can be expressed on T cells at later stages of differentiation [6]. We observed a decrease in the expression of NKG2D in CD3 + , CD56 + and CD56 − T cell subsets in patients with COVID-19 compared to HD, and this reduction was more significant in the ICU group (Figure 4d).…”

“…Thus, NKT-like cells exhibit both adaptive and innate cell properties [3]. This subset includes alpha beta (αβ) T cells, most of which are CD8 + cells at the late stages of differentiation, gamma delta (γδ) T cells, and mucosa-associated invariant T (MAIT) cells [4], all of them characterized by increased effector functions including NK-cell-like cytotoxic potential [5,6]. It has been proposed that CD56 surface expression in CD8 + T cells is closely correlated with their cytotoxic activity [7].…”

Reduced Immunosenescence of Peripheral Blood T Cells in Parkinson’s Disease with CMV Infection Background

“…We did not find any proportional differences in CD56 − T cell and CD56 + T subsets between PD patients and the HD group nor among only CMV-positive individuals from these groups. This fact indicates that more differentiated CD56 + T cells (NKT-like cells), which share some phenotypical and functional features with NK cells [ 37 ], apparently do not participate in PD-mediated response.…”

“…It has been shown that NKG2C + NK cells regulate the expansion of CMV-specific CD8+ T cells: depletion of NKG2C + NK cells augments expansion of CMV-specific CD8 + T cells [ 36 ]. Interestingly, in both CD56 + and CD56 − subsets, most of the NKG2C + T cells had a phenotype of highly differentiated CD8 + T EMRA cells [ 37 ]. Furthermore, an association between CMV-specific CD8 + T-cell responsiveness and the frequency of NKG2C + NK cells expressing CD57 + was detected [ 38 ].…”