Associations between inflammation and senescent/exhaustion markers, CD57, KLRG1, and PD-1 differ in elderly and young

Abstract Background Inflammatory indices such as IL-6 and soluble CD14 are elevated in the elderly, and aging is also associated with immune senescence and exhaustion. Soluble indices of inflammation and immune senescence have independently been associated with mortality and morbidity in the elderly. Whether these pathways are mechanistically linked is not clear. Methods This pilot study examined the relationship of plasma levels of IL-6, IP10, and sCD14 to T cell expression of immune checkpoint markers PD-1, CD57, and KLRG1 inelderly (≥70 years old; n=10) and young (≤40 years old;n=10) participants. Results Elderly participants had elevated plasma levels of IL-6 (p= <0.0001), sCD14 (p=0.0009), and IP10 (p= 0.012) compared to young participants. Surface expression of PD-1 (p= 0.002), CD57 (p= 0.0005), and KLRG1 (p= 0.04) was elevated on memory CD4 T cell in elderly participants. Co-expression of immune checkpoint markers PD-1, CD57, and KLRG1 on CD4 T cells inversely correlated with plasma levels of IL-6 in the elderly; whereas coexpression of checkpoint markers on CD8 T cells positively correlated with plasma levels of IP10 in young participants. Plasma levels of sCD14 positively associated with PD-1 expression on CD4 TEM cells in elderly but inversely correlated with PD-1 expression onCD8 CM and TEM cells in young participants. Conclusion The relationship between soluble indices of inflammation and immune check pointmarker expression varies between elderly and young and between CD4 and CD8 T cells. Further studies are warranted to understand the complex interactions of inflammation and immune senescence and how they contribute tomortality and morbidity in the elderly.