Characterization of KIR + NKG2A + Eomes- NK-like CD8+ T cells and their decline with age in healthy individuals

Abstract

Background: KIR+NKG2A + Eomes+ CD8+ T cells, which are preferentially found with a T_EMRA (CD45RA + CCR7-) phenotype while having the capacity to rapidly produce IFN-γ in response to innate stimulation (IL-12 and IL-18), have been demonstrated to exist in human cord blood and the adult blood circulation. This highly responsive T-cell type was termed NK-like CD8+ T cells due to their capability to act in an innate immune fashion in mice similar to NK cells. However, KIR+NKG2A + CD8+ T cells that are Eomes- represent a small proportion of unconventional T cells that have not been described until now.

Methods: We compare the distribution of the memory phenotypes and senescence-associated markers of two T-cell subsets by multicolor flow cytometry in 10 cord blood samples and 105 healthy individuals (HIs) ranging from 6 to 84 years of age.

Results: We found that the Eomes+ population has a higher differentiation degree than the Eomes- population. T cells in the Eomes- subset show proportionally less T_EMRA phenotypes while instead preferentially displaying a more naïve and T_CM phenotype. Furthermore, the Eomes- population was shown to linearly decrease with age, while the Eomes+ population exhibited more senescence-associated characteristics, such as CD57 expression and loss of CD28.

Conclusion: Overall, the KIR+NKG2A + Eomes- CD8+ T-cell population shares similar characteristics with the Eomes+ population, although with a lower degree of differentiation, lower senescence marker expression, and a proportional decrease with age. Thus, we suspect that KIR+NKG2A + Eomes-CD8+ T cells may represent a less differentiated stage of the NK-like CD8+ T-cell subset.

Keywords: NK-like CD8+ T cells; aging; differentiation; memory T cell.