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

Area of Science:

• Immunology
• T cell subsets
• NK cell receptors

Background:

• Peripheral blood CD56+ T cells are a poorly understood subset.
• NKG2C expression on T cells is associated with differentiation and viral infections.

Purpose of the Study:

• To analyze NKG2C expression in CD56+ T cells.
• To characterize the phenotype and function of CD56+NKG2C+ T cells.
• To investigate the relationship between NKG2C+ T cells and Cytomegalovirus (CMV) infection.

Main Methods:

• Flow cytometry analysis of T cell subsets (CD56+, NKG2C+, CD8+, TEMRA, CD57+, CD45RA+).
• T-cell receptor (TCR) beta-chain repertoire analysis.
• Interferon-gamma (IFN-γ) production assay upon stimulation with human Cytomegalovirus (HCMV) peptides.
• Correlation analysis between T cell and NK cell subsets in HCMV-positive individuals.

Main Results:

• NKG2C+ T cells within both CD56+ and CD56- subsets exhibited a highly differentiated CD8+ TEMRA phenotype.
• CD56+NKG2C+ T cells expressed more NK cell receptors (NKG2D, CD16, KIR2DL2/DL3) and CD57 compared to CD56- counterparts.
• The TCR repertoire of CD56+NKG2C+ T cells showed limited clonotypes, indicating expansion of specific T cell clones.
• NKG2C+ T cells produced minimal IFN-γ in response to HCMV pp65 peptides, potentially due to CD45RA+CD57+ cell presence.
• Activated CD3+NKG2C+ T cells were more frequent in HCMV-positive individuals, correlating positively with NKG2C+ NK cell frequency.

Conclusions:

• NKG2C expression on highly differentiated CD56+ T cells is associated with expanded T cell clones.
• These cells display an activated phenotype and impaired IFN-γ response to HCMV peptides.
• Coordinated development of NKG2C+ T and NK cell subsets may occur under HCMV infection.