Accepted_test

Transcriptional Signatures and Age-Related Changes in CD8+HLA-DR+ Regulatory T Cells

Authors:
Kseniia Matveeva, Department of Immunobiology and Biomedicine, Sirius University of Science and Technology, Sirius, Russia
Semyon Kolmykov, Department of Computational Biology, Sirius University of Science and Technology, Sirius, Russia
Daniil Shevyrev, Resource Center of Cell Technology and Immunology, Sirius University of Science and Technology, Sirius, Russia

Abstract ID: 751

Event: BGRS-abstracts

Sections: Section “Genetics and systems biology of aging”

This study focuses on the transcriptional profiles and age-related changes in CD8⁺HLA-DR⁺ regulatory T cells (CD8⁺Treg), a subset first identified in 2014, which suppress effector T cells and share properties with conventional CD4⁺ regulatory T cells. In according to preliminary experimental data, CD8⁺Treg cells were defined as CD3⁺CD8⁺HLA-DR⁺CD127^low. Our study aims to elucidate their transcriptional signatures and function using open single-cell RNA sequencing data. We analyzed peripheral blood mononuclear cells from 982 donors aged 19-97 years and 99 healthy donors aged 22-75 years, using the Scanpy package for data processing.

Differential expression analysis revealed that CD8⁺Treg cells exhibit increased expression of genes related to MHC II-mediated antigen presentation, cytotoxicity, and cytoskeleton organization. Age-related analysis showed that CD8⁺Treg cells in older individuals (70-97 years) shift towards a terminally differentiated phenotype, characterized by decreased expression of certain cytotoxic protein genes and increased expression of GZMH, without signs of T cell exhaustion. This suggests a transition towards a more differentiated state with age.

The study concludes that CD8⁺Treg cells are a heterogeneous subpopulation of effector CD8⁺ T lymphocytes with increased expression of genes associated with cytotoxicity and antigen presentation. These cells likely mediate suppression through cell-contact dependent cytolysis. In older adults, CD8⁺Treg cells show a shift towards a terminally differentiated phenotype, indicating changes in their functional properties with age.