Natural killer cells appear to be the ground zero for the immune dysfunction found in chronic fatigue syndrome. These cells are, as their name implies, killers. They’re called “natural” killer cells because in contrast to cytotoxic T-cells which need to be activated to fight infections, NK cells are always “on”; they’re always prowling the bloodstream for damaged or infected cells. Apparently, when you constitute the first line of immune defense in the human body, you don’t take time off.
Unfortunately, in ME/CFS NK cell’s bark is worse than their bite. Studies have consistently shown that the NK cells in many ME/CFS patients appear to be lethargic and burnt out. They simply don’t kill as many infected cells as healthy natural killer cells do.
The NK cell dysfunction in chronic fatigue syndrome has been evident for years, but an even more insidious problem may be present. Several studies now suggest that the powerful killers featured in the adaptive or late immune response – the cytotoxic T-cells – have the same problem in ME/CFS as do the NK cells.
If that’s true, then both the early and late immune responses are inhibited in ME/CFS.
Novel Antiviral / Anticancer Agent Found
- Science DOI: 10.1126/science.aaa7516. The protein LEM promotes CD8+ T cell immunity through effects on mitochondrial respiration. Isobel Okoye, Lihui Wang, Katharina Pallmer, Kirsten Richter2, Takahuru Ichimura,…..Philip G. Ashton-Rickardt1,3,‡
Unfortunately no readily available drugs are able to improve NK or T-cell functioning. A recent breakthrough could change that, though. Imperial College researchers in London uncovered the presence of a novel protein that appears to dramatically boost both antiviral and anti-cancer defenses.
It took a large team six years. First, they found a strain of mice with dramatically enhanced T-cell responses that was able to more quickly fight off viruses and cancer. Using sophisticated gene screening they uncovered the gene responsible for the mice’s extraordinarily effective immune system. Then they found a heretofore undiscovered protein that the gene was producing. They called it “lymphocyte expansion molecule” or LEM.
Interestingly, given the current interest in the mitochondria in ME/CFS, that protein turned out to be a mitochondrial booster. LEM effectuates cytotoxic T-cell responses by turning on the mitochondria in cytotoxic T-cells.
With the aim of bringing gene therapy to improve immunity to the market the London team has filed two patents on ways to enhance LEM in humans. Mouse trials will begin quickly and they hope to begin human trials within three years.
The findings may eventually result in a new approach to fighting viruses and/or cancer.
“This study has identified the novel protein LEM and unlocked an unexpected way of enhancing the ability of our immune system to fight viruses or cancers. This is based on the ability of the protein LEM to regulate specific energy circuits, and particularly mitochondrial respiration, in a subset of white blood cells known as cytotoxic T cells. This discovery has immediate consequences for the delivery of innovative therapeutic approaches to cancer.” Claudio Mauro, Ph.D.
The relevance of this finding to ME/CFS is unclear. The news accounts of the study focused on LEM’s ability to increase T-cell proliferation. A recent study suggested that T-cell proliferation is inhibited in ME/CFS, but the biggest concern in ME/CFS is reduced cytotoxic T-cell functioning. The reference in LEM studies abstract to increased “effector” functioning, however, could suggest cytotoxic T-cell killing ability was enhanced as well. If that’s true the protein could have direct relevance for ME/CFS.
NK Cell Connection?
We don’t know that LEM has the same effects on NK cells as it does on T-cells. Both cells, though, employ the same type of killing machinery to remove infected cells and, perhaps importantly, similar “signalling cascades” to control the “effector functions” in T-cells.
Reduced NK functioning is not the result of low NK cell numbers in ME/CFS. It’s possible, though, that increasing NK cells could be helpful in the same way that increasing cytotoxic T-cells are projected to be. Even healthy humans have trouble generating enough cytotoxic T-cells to fight off infections or cancer. The London hopes this new protein will help patients to get rid of lingering viruses or tumors.
The other major caveat is that the finding was in mice. As Mark Davis put it – mice diverged from humans 60 million years ago. They have four legs we have two. Their hearts beat 400 times a minute. Ours beat 60 times a minute. They’re different. That doesn’t mean they’re not useful; many of the immune discoverers for humans have taken place in mice, but they are different.
There are too many if’s and’s or but’s to determine what relevance, if any, this finding has for ME/CFS. The discovery of a novel protein that plays a key role in the immune systems ability to fight off viruses and cancer is encouraging, however, in and of itself. It underscores how much yet there is to learn about the immune system and what surprises may be in store as researcher dig deeper and deeper into this complex system.
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