Immune aging and NK cells – oh, and let’s clear up a few things about CD57

Natural Killer cells. (Science Photo Library)

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.

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7 Responses to Immune aging and NK cells – oh, and let’s clear up a few things about CD57

  1. Anna Ward says:

    Dear Sirid, i was wondering if you might be able to help a lay person better understand CD57 natural killer cells. I understand that CD57 + natural killer cells can be indicative of the state of a persons immune system but cannot be used to diagnose particular illnesses. What i am interested to know is whether, in your opinion, a person can have a low CD57+ NK and not be chronically ill. In other words, is it possible for a healthy person to have a low CD57+ NK result? Many thanks and best wishes, Anna

    • Great question, Anna. I guess we first we need to qualify what constitutes a “low” CD57 count. Stricker’s original paper that laid claim to a link between CD57 count and chronic Lyme noted that control individuals had a CD57 count between 60 and 360. Marques and colleagues tested 9 healthy controls and their range was about 40-250. Similarly, A Chinese study of 16 sedentary healthy men indicated a CD57 count as low as around 45-50. Marcos (1997) indicated that bulimic individuals have significantly lower CD57 counts than their healthy counterparts (not that bulimic patients constitute “healthy” individuals, but FYI).

      So, I don’t find anything that suggests that healthy people would have a CD57 count much lower than 40 or 45.

  2. Brenda Hawley says:

    I have had 3 CD-57 tests in the last 18 months trying to find a cause for extreme fatigue. The tests were 10,11 and 14. I am a 61 year old female distance runner who was in incredible shape prior to the exhaustion symptoms. I was told the low CD-57 was proof of lyme disease and was on antibiotics for 18 months with no positive result. Are you saying that a low CD-57 does not mean lyme? Does it mean some kind of infection- bacterial or virus?

    • Brenda, there is no evidence that a low CD57 count alone diagnoses Lyme. Many healthcare practitioners I’ve spoken to in the past year agree with me, and even Dr. Stricker, who published compelling data about the link between Lyme disease and low CD57 count, doesn’t believe this link is exclusive to Lyme. Unfortunately, scientists are still trying to understand WHAT exactly a low CD57 count can be indicative of. My hunch is it’s not one particular type of infectious organism.

  3. Jennifer Reynolds says:

    I was exposed to toxic mold for a little over 6 months. While being exposed doctors were unable to identify what was causing me to get sick so I went to an immunologist. The first test my CD57 level was 22. I have now been out of the toxic mold environment for 4 months and I have my CD57 tested again, which is now at 15. The doctor thinks its being caused by being exposed to toxic mold and doesn’t seem concerned. Can toxic mold cause CD57 levels to decrease? I am not sure where to go from here.

    • Bradley Bush, N.D. says:

      It is possible that CD57 levels can increase due to an environmental exposure. It is not a specific test. There are some labs that specialize in environmental and human mold testing. I would consult with your health care provider to explore your options.

  4. Dana Monk says:

    I have a low CD57 count and high HHv6 count. I have breast implants could these be causing my problems?

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