Sizes of Immune Cell Subsets Correlate with Human Mortality
The immune system is made up of many different cell types. Further, distinct populations within those types exhibit a varied range of behaviors. The molecular damage and resulting cellular dysfunction of aging produces complex changes in the immune system, as is the case for all of the complex biological systems of the body and brain. Aging leads to a reduced ability to defend against pathogens and increased chronic inflammation, but understanding exactly how observed changes in cell behavior lead to that outcome remains a work in progress. Here, researchers use a large set of study data to investigate associations between the size of specific immune cell populations and human mortality.
Age-related immunosenescence is characterized by changes in immune cell subsets and is associated with mortality. In this study, we found that T cells and natural killer (NK) cells with low expression of CD56 were inversely associated with mortality while neutrophils were positively associated with mortality. In addition, we found myeloid dendritic cells to be nominally associated with a reduced odds of mortality, and CD4+ effector memory T cells and IgD- memory B cells to be nominally associated with increased mortality odds.
Several previous studies have shown a positive association between neutrophils and mortality and our study confirmed these previous findings. The number of neutrophils are preserved in older adults though their phagocytic ability is impaired. Furthermore, since neutrophils are pro-inflammatory, higher numbers of neutrophils in older adults may increase the odds of mortality. NK cells cytotoxicity and IFN-γ production decreases in old age, and low cytotoxicity is associated with increased morbidity and mortality. NK LO cells have significantly higher cytotoxicity than NK Hi cells. Hence, the observed inverse association with mortality was consistent with the biological activity of this NK cell subtype.
A higher percentage of myeloid subset of dendritic cells was associated with reduced mortality, which was consistent with previous studies showing that dendritic cells mediate antitumor immune responses, and were used in immunotherapies and vaccinations that resulted in improved survival of cancer patients. The absolute count of T cells decreases with age, and this decrease especially affects naïve subset (Tn). This alters the T cell repertoire, compromising their ability to mediate effective immune responses, and thus increasing the odds of mortality. The inverse association seen for total T cells in this study was in line with a previous study on hemodialysis patients.
As immunosenescence is characterized by accumulation of memory and effector T cells, a positive association between CD4+ effector memory T subset and mortality was consistent with the known distribution of this immune subset in older adults. Of note, we have previously shown that CMV seropositivity and not age was the predominant determinant of CD4+ effector memory T levels suggesting that the association between some of the immune cell subsets and mortality may be primarily driven by environmental exposures as compared to age-related processes.