image_3_CD8+HLADR+ Regulatory T Cells Change With Aging: They Increase in Number, but Lose Checkpoint Inhibitory Molecules and Suppressive Function.tif
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
10.3389/fimmu.2018.01201.s003
https://frontiersin.figshare.com/articles/figure/image_3_CD8_HLADR_Regulatory_T_Cells_Change_With_Aging_They_Increase_in_Number_but_Lose_Checkpoint_Inhibitory_Molecules_and_Suppressive_Function_tif/6427469
<p>CD4<sup>+</sup> 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<sup>+</sup>human leukocyte antigen–antigen D related (HLADR)<sup>+</sup> 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<sup>+</sup>HLADR<sup>+</sup> 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<sup>+</sup>HLADR<sup>+</sup> 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<sup>−</sup> counterparts. They also have the capacity to inhibit the proliferation of autologous peripheral blood mononuclear cells. This suppressive activity is, however, decreased when CD8<sup>+</sup>HLADR<sup>+</sup> T cells from elderly persons are analyzed. In accordance with this finding, CD8<sup>+</sup>HLADR<sup>+</sup> 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<sup>+</sup> 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.”</p>
2018-06-04 04:10:02
CD8+ T cells
CD8+human leukocyte antigen–antigen D related+
aging
checkpoint inhibitory molecules
regulatory T cells