Transcriptional Analysis of Total CD8+ T Cells and CD8+CD45RA- Memory T Cells From Young and Old Healthy Blood Donors

Georgiana Toma; Ioana Maria Lemnian; Eliza Karapetian; Ivo Grosse; Barbara Seliger

doi:10.3389/fimmu.2022.806906

Transcriptional Analysis of Total CD8⁺ T Cells and CD8⁺CD45RA^- Memory T Cells From Young and Old Healthy Blood Donors

Front Immunol. 2022 Jan 27:13:806906. doi: 10.3389/fimmu.2022.806906. eCollection 2022.

Authors

Georgiana Toma¹, Ioana Maria Lemnian^{2

3}, Eliza Karapetian¹, Ivo Grosse^{2

4}, Barbara Seliger^{1

5}

Affiliations

¹ Institute for Medical Immunology, Martin-Luther University Halle-Wittenberg, Halle, Germany.
² Institute for Computer Science, Martin-Luther University Halle-Wittenberg, Halle, Germany.
³ Institute for Human Genetics, Martin-Luther University Halle-Wittenberg, Halle, Germany.
⁴ German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany.
⁵ Department for Therapeutics, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.

Abstract

Memory CD8⁺ T cells accumulate with aging, while the naïve T cell compartment decreases, leading to an increased susceptibility to infections and a decreased vaccine efficiency. To get deeper insights into the underlying mechanisms, this study aims to determine the age-dependent expression profile of total versus memory CD8⁺ T cells from young and old donors. Total CD8⁺ and CD8⁺CD45RA^- memory T cells isolated from young (<30 years) and old (>60 years) donors were stimulated with anti-CD3 and anti-CD28 antibodies for 48h before analyzing the cytokine secretion and activation markers by flow cytometry and changes in the expression profiles using RNA sequencing. Gene ontology (GO) term enrichment analyses were performed for up-regulated and uniquely expressed transcripts identified in the T cell populations of both age groups. Total and memory CD8⁺ T cells from old donors expressed significantly higher CD25 levels and have an increased cytokine secretion. While approximately 1,500 up-regulated transcripts were identified in all groups, CD8⁺CD45RA^- memory T cells of old donors had approximately 500 more uniquely expressed transcripts. Four GO terms related to the JAK-STAT pathway were identified for up-regulated transcripts in the total CD8⁺ T cells of old donors, whereas CD8⁺CD45RA^- memory T cells GO terms related to adjacent pathways, like JNK and MAPK/ERK, were found. Additionally, the unique transcripts of CD8⁺CD45RA^- memory T cells of old donors were related to the JNK, MAPK and IL-12 pathways. For both T cell populations of the old donors, cytokine and JAK-STAT pathway transcripts were up-regulated. Thus, an age-dependent effect was observed on the transcriptomes of total and memory CD8⁺ T cells. The CD8⁺ CD45RA^- memory T cells from old donors maintained the increased cytokine secretion of the total CD8⁺ T cell population and the increased JAK-STAT pathway transcripts, which have an impact on inflammation and senescence.

Keywords: CD8+; GO terms; JAK/STAT pathway; RNA sequencing; T cells; aging; memory T cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Age Factors
Aged
Aging* / immunology
Blood Donors* / statistics & numerical data
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / classification
CD8-Positive T-Lymphocytes / immunology*
Cytokines
Female
Flow Cytometry
Gene Expression Profiling / methods*
Healthy Volunteers / statistics & numerical data
Humans
Immunologic Memory / immunology*
Leukocyte Common Antigens / genetics*
Lymphocyte Count
Male
Memory T Cells / immunology*
Middle Aged
Young Adult

Substances

Cytokines
Leukocyte Common Antigens
PTPRC protein, human