As I mentioned in my previous entry, aging of the immune system – or immunosenescence – affects many kinds of immune cells. Since I recently discussed natural killer (NK) cells, I’ll add a few comments about immunosenescence regarding these cells specifically. (For a good review, see the paper by Gayoso et al., 2011.
First, a quick primer.
- NK cells are critical to innate immunity (those rapid, nonspecific immune responses). They can tell “self” from “non-self” which lets them recognize virus-infected cells and certain cancer cell types.
- NK cells can be divided into two main subsets.
- CD56(bright) NK cells that produce cytokines which activate and enhance the actions of other white blood cells
- CD56(dim) NK cells that are primarily known for their ability to lyse and kill “non-self” cells, also known as cytotoxicity.
- There is a continuum of NK cell differentiation (e.g. from CD56(bright) to CD56(dim). At the far end of this continuum is the CD56(dim)CD57+ NK cell subset that is highly differentiated, probably terminally so. Keep in mind that “terminal” here doesn’t mean that CD57+ NK cells are dying – just that they will no longer differentiate into any other functional subset. (Here I want to kindly thank my former colleague Dr. Lewis Lanier for his insights and point you to a recent paper from his lab about CD57+ NK cells (Lopez-Verges, 2010).)
As offered by NeuroScience, Inc., tests can assess people’s NK cell status by (1) counting them, and (2) by measuring their cytotoxic activity. As we discussed last time, immunosenescence doesn’t necessarily track with chronological age. Healthy centenarians have exhibited an overall increase in their NK cell count, and no decrease in NK cell cytotoxic activity. In contrast, unselected elderly populations (i.e., all comers, regardless of health status) show evidence of reduced NK cell count and cytotoxic activity. This can be a predictive biomarker of overall health risk, with at least one report indicating that individuals with a low NK cell count have an increased mortality risk compared to individuals with high NK cell count (Remarque & Pawelec, 1998, as cited in Gayoso et al.). Evidence similarly points to the association of low NK cell activity with infections and degenerative diseases such as atherosclerosis (Bruunsgaard, 2001).
We are beginning to understand the reason for these differences: During immunosenescence, an important shift in NK cell subsets occurs – there is a decline in cytokine-producing CD56(bright) NK cells, and an increase in cytotoxic CD56(dim)CD57+ NK cells.
How this contributes to overall immunosenescence, and increased health issues, is that the loss of cytokine-producing CD56(bright) NK cells likely means a reduction in the cytokine signals that are critical for activating other immune cells, such as macrophages, dendritic cells, and T cells. This could result in a reduced ability to effectively conquer infectious microbes.
A final comment regarding CD57: I urge anyone who orders CD57 tests on their patients to take the patient’s age into consideration when interpreting the results. Since it is a general marker of NK cell terminal differentiation, I’ll also wager that there is nothing pathogen-specific about a CD57 count! It cannot and should not be used to diagnose Lyme disease, XMRV, or any other specific infection, though I don’t reject the possibility that an extremely low CD57+ NK cell count may indicate some sort of pathology.