Inflammageing: increase in polymorphonuclear myeloid-derived suppressor cells in aged healthy individuals

Introduction: Myeloid-derived suppressor cells (MDSCs) are immature HLA‑DR^low/‑CD11b⁺CD33⁺ myeloid cells, which are elevated in various human disease states that involve abnormal haemopoiesis and act mainly through suppressing T-cell responses. They are divided into two subpopulations, the CD15⁺ (granulocytic) and the CD14⁺ (monocytic) cells. We have previously shown that the number and functionality of MDSCs in chronic idiopathic neutropenia (CIN) are altered, contributing to a possible primary bone marrow (BM) defect and to the pathogenesis of the condition. Moreover, MDSCs are proposed in a few studies to take part in ageing, in concordance with the novel theory of inflammageing. Thus, we further suggest that, in healthy individuals, their numbers increase with age through impaired myelopoiesis.

Methods: MDSC subsets were quantitated by flow cytometry in the peripheral blood mononuclear cells (PBMCs) of 70 healthy individuals (21-73 years old), using the combination of CD33PC7/CD15PC5/HLA-DRECD/CD14PE/CD11bFITC monoclonal antibodies and the Kaluza® analysis software. Statistical analysis was performed using the Spearman’s rank correlation coefficient and the GraphPad® software. The suppression of T-cell proliferation by MDSCs was estimated in five selected cases by comparing carboxy-fluorescein succinimidyl ester (CFSE) staining of the anti-CD3/anti-CD28-activated T-cells between PBMCs and CD33-depleted PBMCs after 3 days of culture.

Results: PMN-MDSCs (1.75% of PBMCs ± 2.55, mean±standard deviation) showed a statistically significant positive correlation with age (r=0.24, p=0.04), while neither M-MDSCs (3.97% of PBMCs ± 2.96) nor the total population of MDSCs (PMN-MDSCs plus M-MDSCs) (6.40% of PBMCs ± 2.17) showed a statistically significant correlation with age. MDSCs displayed the capacity to suppress T-cell proliferation, as was indicated by the T-cell generations in culture experiments in the presence or absence of MDSCs, irrespective of the age of the individual.

Conclusions: In conclusion, in our study population, PMN-MDSCs increase in older individuals, contributing to the process of ageing, while they retain their immunosuppressive capacity.