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CD8 + HLADR + Regulatory T Cells Change With Aging: They Increase in Number, but Lose Checkpoint Inhibitory Molecules and Suppressive Function.
- Source :
-
Frontiers in immunology [Front Immunol] 2018 Jun 04; Vol. 9, pp. 1201. Date of Electronic Publication: 2018 Jun 04 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- CD4 <superscript>+</superscript> regulatory T cells have been intensively studied during aging, but little is still known about age-related changes of other regulatory T cell subsets. It was, therefore, the goal of the present study to analyze CD8 <superscript>+</superscript> human leukocyte antigen-antigen D related (HLADR) <superscript>+</superscript> T cells in old age, a cell population reported to have suppressive activity and to be connected to specific genetic variants. We demonstrate a strong increase in the number of CD8 <superscript>+</superscript> HLADR <superscript>+</superscript> T cells with age in a cohort of female Sardinians as well as in elderly male and female persons from Austria. We also show that CD8 <superscript>+</superscript> HLADR <superscript>+</superscript> T cells lack classical activation molecules, such as CD69 and CD25, but contain increased numbers of checkpoint inhibitory molecules, such as cytotoxic T lymphocyte-associated antigen 4, T cell immunoglobulin and mucin protein-3, LAG-3, and PD-1, when compared with their HLADR <superscript>-</superscript> counterparts. They also have the capacity to inhibit the proliferation of autologous peripheral blood mononuclear cells. This suppressive activity is, however, decreased when CD8 <superscript>+</superscript> HLADR <superscript>+</superscript> T cells from elderly persons are analyzed. In accordance with this finding, CD8 <superscript>+</superscript> HLADR <superscript>+</superscript> T cells from persons of old age contain lower percentages of checkpoint inhibitory molecules than young controls. We conclude that in spite of high abundance of a CD8 <superscript>+</superscript> regulatory T cell subset in old age its expression of checkpoint inhibitory molecules and its suppressive function on a per cell basis are reduced. Reduction of suppressive capacity may support uncontrolled subclinical inflammatory processes referred to as "inflamm-aging."
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Antigens, CD metabolism
Austria
CD8 Antigens metabolism
CTLA-4 Antigen metabolism
Cell Proliferation
Cohort Studies
Female
HLA-DR Antigens metabolism
Hepatitis A Virus Cellular Receptor 2 metabolism
Humans
Immune Tolerance
Italy
Lymphocyte Activation
Male
Middle Aged
Programmed Cell Death 1 Receptor metabolism
Young Adult
Lymphocyte Activation Gene 3 Protein
Aging immunology
Inflammation immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 29915580
- Full Text :
- https://doi.org/10.3389/fimmu.2018.01201