Age-related decrease of miRNA-92a levels in human CD8+ T-cells correlates with a reduction of naïve T lymphocytes

Abstract

MicroRNA (miR)-17-92a expression plays a crucial role in lymphocyte ontogeny. We therefore set out to determine miR-92a expression levels in peripheral blood lymphocytes from healthy subjects to ascertain any association between these levels and ageing. We found a positive correlation between the miR-92a expression level and the percentages of RO-CD8+CD27+ (P = 0.0046) and CD3+CD8+CD62L+ (P = 0.0011). This suggests that the majority of miR-92a of CD8+ T cells is derived from naïve cells, and the miR-92a expression level in CD8+ T cells declines progressively with age. These results indicate that the age-related attrition of naïve T cells is linked to a reduction of miR-92a in human T -lymphocytes. Therefore, we should careful attention when evaluating human miRNA levels in T lymphocytes to use normal control values.

Longitudinal Examination of the Intestinal Lamina Propria Cellular Compartment of Simian Immunodeficiency Virus-Infected Rhesus Macaques Provides Broader and Deeper Insights into the Link between Aberrant MicroRNA Expression and Persistent Immune Activation

“…These in vivo findings are consistent with three previous reports that showed the downregulation of the miR-17-92 cluster during CD8 ϩ T-cell differentiation and activation in vitro (25,26,34,35). Interestingly, miR-181a expression decreased at both 90 and 180 dpi.…”

Inhibition of MicroRNA-92a Prevents Endothelial Dysfunction and Atherosclerosis in Mice

“…Atherosclerosis development is tightly controlled by both innate and adaptive immunity. 36 Although miR-92a expression had been previously reported in T lymphocytes, 37 we did not observe any effect of miR-92a inhibition on immune parameters, including monocyte, T, and B cell counts as well as immune cell activation. These observations reinforce our conclusion that the antiatherogenic effects observed after miR-92a blockade resulted from protection against endothelial dysfunction.…”

Reply to Shin and Bayry on “An age-related decline of CD62L and vaccine response: a role of microRNA 92a?”

“…For both age groups, the percentage of CD3 + CD4 + CD62L + cells were at ~30% while the CD3 + CD8 + CD62L + cells constituted ~18%, quite similar to the level reported by Ohyashiki et al for individuals in their early 20s. 2 Taken together, we are hesitant to agree that the CD62L expression in general is significantly reduced as a consequence of increasing age in the interval from young to elderly. Indeed, in a broader context, age-related attenuation of receptor expression and their functions in lymphocytes identified such phenomena only when comparing groups with relatively extreme age differences unlike the donors in our study.…”

“…However, as part of their correlation analyses Ohyashiki et al found an approximately 4-fold reduction in the percentage of CD3 + CD8 + CD62L + T lymphocytes in individuals in their late fifties (at ~5%) compared with individuals in the early 20s (at ~18%). 2 De Martinis et al also reported a significant age-related reduction in the percentage of CD62L expressing T lymphocytes, but only 1.5-fold (from 81% to 53%) when comparing the naïve lymphocytes from a group of young individuals with a mean age of 30 y (n = 10) with the same subset from a group of very elderly individuals with a mean age of 90 y (n = 10). 3 In the case of central memory T cells, the reduction was only 1.2-fold (from 64% to 55%).…”

“…2 Correlations involving the micro RNA miR-92a further prompted Ohyashiki et al to suggest miR-92a as part of the regulatory potential controlling CD62L expression.…”