Accepted_test

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.