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CD8+HLADR+ Regulatory T Cells Change With Aging: They Increase in Number, but Lose Checkpoint Inhibitory Molecules and Suppressive Function

2018; Frontiers Media; Volume: 9; Linguagem: Inglês

10.3389/fimmu.2018.01201

1664-3224

Stella Lukas Yani, Michael Keller, Franz Leonard Melzer, Birgit Weinberger, Luca Pangrazzi, Sieghart Sopper, Klemens Trieb, Monia Lobina, Valeria Orrù, Edoardo Fiorillo, Francesco Cucca, Beatrix Grubeck‐Loebenstein,

Cancer Immunotherapy and Biomarkers

CD4+ 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+HLADR+ 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+HLADR+ 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+HLADR+ T cells lack classical activation molecules such as CD69 and CD25, but contain increased numbers of checkpoint inhibitory molecules such as CTLA-4, TIM-3, LAG-3 and PD-1, when compared with their HLADR- counterparts. They also have the capacity to inhibit the proliferation of autologous PBMCs. This suppressive activity is, however, decreased when CD8+HLADR+ T cells from elderly persons are analyzed. In accordance with this finding, CD8+HLADR+ 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+ 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".