Investigating age-related dynamics and transcriptional signatures of CD8⁺HLA-DR⁺ regulatory T lymphocytes: perspectives in understanding immune system aging

The ability of the CD8⁺HLA-DR⁺ regulatory T lymphocytes population to regulate the immune response was first described several years ago. It is known that the suppressive effects of these cells depend on intercellular interactions and are mediated by the expression of checkpoint inhibitor molecules such as CTLA-4, TIM-3, PD-1 and LAG-3. The CD8⁺HLA-DR⁺ regulatory T cells also share some properties with conventional CD4⁺ regulatory T lymphocytes. Nevertheless, the characteristics and function of this subpopulation remain poorly understood. Furthermore, studying the properties of CD8⁺HLA-DR⁺ regulatory T cells becomes relevant in the light of general age-associated changes in the human immune system and the increased sensitivity of CD8⁺T lymphocytes to these changes. Therefore, the aim of this study was to investigate the age dynamics and search for transcriptional signatures of the CD8⁺HLA-DR⁺ regulatory T cells. For this purpose, flow cytometric analysis of peripheral blood mononuclear cells from 18 donors aged 21 to 85 years was performed. Bioinformatic analysis of single-cell RNA sequencing data was carried out to search for signatures. It was found that CD8⁺HLA-DR⁺ regulatory T cells accumulate with age. The transcriptional signatures of this population consist of genes involved in antigen presentation and cytotoxicity, along with a decrease in the expression of genes encoding proteins of activating protein 1 complex. These data suggest mechanisms of suppressor function of CD8⁺HLA-DR⁺ regulatory T lymphocytes associated with the ability of these cells to present antigens and perform cytotoxic activity against effector T lymphocytes. The accumulation of the studied cells may imply a potential influence of CD8⁺HLA-DR⁺ regulatory T lymphocytes on the efficiency of adaptive immune response in the aging. Further studies of this population may provide insights into its role in age-related changes in the immune system and develop strategies to improve the immune response in the elderly.

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