CMV-specific clonal expansion of Th1, GZMK⁺ CD8⁺, and TEMRA T cells revealed by human PBMC single cell profiling

Area of Science:

• Immunology
• Gerontology
• Virology

Background:

• Cytomegalovirus (CMV) is a common herpesvirus establishing lifelong latency.
• Its prevalence increases with age, but its systemic impact on the aging immune system is not fully understood.

Purpose of the Study:

• To investigate the systemic impact of Cytomegalovirus (CMV) on the aging immune system.
• To identify specific immune cell alterations associated with CMV serostatus in older adults.
• To develop a computational tool for predicting CMV serostatus from single-cell data.

Main Methods:

• Single-cell RNA-sequencing of circulating immune cells from healthy older adults (CMV(+) and CMV(-)).
• Validation of key findings using flow cytometry.
• Development and validation of a machine learning classifier (CMVerify) for CMV serostatus prediction.

Main Results:

• CMV(+) individuals showed significant expansion of adaptive immune cells (CD4+, CD8+ TEMRA T, GZMK+ CD8+ T, γδ T, atypical B cells).
• Innate immune cells like monocytes and dendritic cells were largely unchanged.
• Adaptive NK cells (KLRC2+) increased, while CD56dim NK cells decreased in CMV(+) individuals.
• CMVerify achieved 97% accuracy in predicting CMV serostatus across datasets.

Conclusions:

• Cytomegalovirus (CMV) infection induces extensive immune remodeling in the elderly.
• Specific adaptive and innate immune cell populations are altered by CMV in older adults.
• CMV status is a critical factor to consider in aging immunology research, and CMVerify aids in its assessment.