CMV-specific clonal expansion in human Th1 and GZMK⁺ CD8⁺ T cells.
19 affiliations
- 1The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA.
- 2University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
- 3Health Sciences North Research Institute, NOSM University, Sudbury, ON, P3E 2H3, Canada.
- 4Department of Medicine, McMaster University, Hamilton, ON, L8S 4L8, Canada.
- 5GRECC, Durham VA Health Care System, Durham, NC, 27705, USA.
- 6Department of Medicine and Duke Center for the Study of Aging and Human Development (Aging Center), Duke University School of Medicine, Durham, NC, 27705, USA.
- 7Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
- 8Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
- 9Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
- 10The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
- 11Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
- 12The Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
- 13Department of Pathology, Yale School of Medicine, New Haven, CT, 06510-3222, USA.
- 14The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA. [email protected].
- 15Immunoledge LLC, Montclair, NJ, 07042, USA. [email protected].
- 16University of Connecticut School of Medicine, Farmington, CT, 06030, USA. [email protected].
- 17UConn Center On Aging, University of Connecticut School of Medicine, Farmington, CT, 06030, USA. [email protected].
- 18The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA. [email protected].
- 19Institute for Systems Genomics, University of Connecticut Health Center, Farmington, CT, 06030, USA. [email protected].
Abstract
Background
Cytomegalovirus (CMV) is a common herpesvirus that establishes lifelong latency and becomes increasingly prevalent with age. To systematically delineate CMV-associated immune remodeling at single-cell resolution, we analysed six human cohorts (including two newly established cohorts) using single-cell RNA sequencing, T cell receptor (TCR) sequencing, and flow cytometry.Results
We identified novel CMV-associated changes in cell frequencies, including increases in GZMK⁺ CD8⁺ T cells and atypical B cells, and a reduction in CD56dim NK cells, in addition to the canonical expansion of CD4⁺/CD8⁺ TEMRA and adaptive NK cells. Longitudinal profiling of an individual who seroconverted revealed rapid CMV-driven shifts in circulating immune cell frequencies. Leveraging a recently published CMV-specific TCRβ database, combined with predictive modeling (CMVerify), we identified novel CMV-specific clonal expansions that were reproduced across two independent cohorts. In the CD8⁺ lineage, CMV-specific clones were enriched in GZMK⁺ CD8⁺ T cells and CD8⁺ TEMRA cells, whereas in the CD4⁺ lineage, Th1 cells showed clonal expansion alongside CD4⁺ TEMRA cells.Conclusions
This multi-cohort integrative study defines the cellular and clonal signatures of latent CMV in humans and identifies GZMK⁺ CD8⁺ T cells and Th1 cells as previously underappreciated components of the CMV response.
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BibTeX
@article{grabauskas2026cmvspecific,
title = {{CMV-specific clonal expansion in human Th1 and GZMK⁺ CD8⁺ T cells.}},
author = {Titas Grabauskas and Luke Trinity and Chris P Verschoor and Djamel Nehar-Belaid and Radu Marches and Giray Eryilmaz and Avinash S Mahajan and Sathyabaarathi Ravichandran and Asa Thibodeau and Emilie Picard and Chia-Ling Kuo and Kenneth E Schmader and Cathleen Colon-Emeric and Heather E Whitson and Silke Paust and Adolfo García-Sastre and Gur Yaari and Jacques Banchereau and George A Kuchel and Duygu Ucar},
journal = {Genome biology},
year = {2026},
month = aug,
doi = {10.1186/s13059-026-04198-5},
url = {https://europepmc.org/article/MED/42958310},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - CMV-specific clonal expansion in human Th1 and GZMK⁺ CD8⁺ T cells.
AU - Titas Grabauskas
AU - Luke Trinity
AU - Chris P Verschoor
AU - Djamel Nehar-Belaid
AU - Radu Marches
AU - Giray Eryilmaz
AU - Avinash S Mahajan
AU - Sathyabaarathi Ravichandran
AU - Asa Thibodeau
AU - Emilie Picard
AU - Chia-Ling Kuo
AU - Kenneth E Schmader
AU - Cathleen Colon-Emeric
AU - Heather E Whitson
AU - Silke Paust
AU - Adolfo García-Sastre
AU - Gur Yaari
AU - Jacques Banchereau
AU - George A Kuchel
AU - Duygu Ucar
PY - 2026
DA - 2026/08/04
JO - Genome biology
DO - 10.1186/s13059-026-04198-5
UR - https://europepmc.org/article/MED/42958310
AB - Background Cytomegalovirus (CMV) is a common herpesvirus that establishes lifelong latency and becomes increasingly prevalent with age. To systematically delineate CMV-associated immune remodeling at single-cell resolution, we analysed six human cohorts (including two newly established cohorts) using single-cell RNA sequencing, T cell receptor (TCR) sequencing, and flow cytometry.Results We identified novel CMV-associated changes in cell frequencies, including increases in GZMK⁺ CD8⁺ T cells and atypical B cells, and a reduction in CD56dim NK cells, in addition to the canonical expansion of CD4⁺/CD8⁺ TEMRA and adaptive NK cells. Longitudinal profiling of an individual who seroconverted revealed rapid CMV-driven shifts in circulating immune cell frequencies. Leveraging a recently published CMV-specific TCRβ database, combined with predictive modeling (CMVerify), we identified novel CMV-specific clonal expansions that were reproduced across two independent cohorts. In the CD8⁺ lineage, CMV-specific clones were enriched in GZMK⁺ CD8⁺ T cells and CD8⁺ TEMRA cells, whereas in the CD4⁺ lineage, Th1 cells showed clonal expansion alongside CD4⁺ TEMRA cells.Conclusions This multi-cohort integrative study defines the cellular and clonal signatures of latent CMV in humans and identifies GZMK⁺ CD8⁺ T cells and Th1 cells as previously underappreciated components of the CMV response.
SN - 1474-7596
SN - 1474-760X
ER -