Summary of NK and T cell discussions

Pyrrhus

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Since scientific studies on the lymphocytes called Natural Killer (NK) cells and CD8+ T cells in ME have provided conflicting results, I just wanted to start a thread to summarize in one place all discussions on this issue.

Hopefully, by listing all discussions in one place, it will be easier to see a bigger picture, if there is one.
(Note that CD8+ T cells are also called Cytotoxic T cells.)

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Discussions about lymphocytes such as NK cells or T cells:

Biomarkers in CFS: Natural Killer function (Fletcher/Klimas 2010)
https://forums.phoenixrising.me/thr...l-killer-function-fletcher-klimas-2010.11051/

Cytotoxic lymphocyte microRNAs as prospective biomarkers for CFS/ME (Brenu, Staines, Marshall-Gradisnik et al., 2012)
https://forums.phoenixrising.me/threads/new-phanu-study-on-microrna-markers.17324/

Longitudinal investigation of natural killer cells and cytokines in CFS/ME (Brenu, Staines, Marshall-Gradisnik et al., 2012)
https://forums.phoenixrising.me/thr...l-killer-cells-and-cytokines-in-cfs-me.16125/

Screening NK-, B- and T-cell phenotype and function in patients suffering from CFS. (Curriu et al., 2013)
https://forums.phoenixrising.me/thr...s-suffering-from-chronic-fatigue-syndr.22476/

Increased expression of activation antigens on CD8+ T lymphocytes in ME/CFS: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto)immune, leaky gut, oxidative and nitrosative stress biomarkers (Maes et al., 2015)
https://forums.phoenixrising.me/thr...mphocytes-in-myalgic-encephalomyelitis.42118/

Unperturbed cytotoxic lymphocyte phenotype and function in ME/CFS patients (Theorell et al., 2017)
https://forums.phoenixrising.me/thr...ocyte-phenotype-and-function-in-me-cfs.52458/

Association of T and NK Cell Phenotype With the Diagnosis of ME/CFS (Rivas et al., 2018)
https://forums.phoenixrising.me/thr...e-diagnosis-of-me-cfs-rivas-et-al-2018.60032/

Longitudinal associations of lymphocyte subsets with clinical outcomes in CFS (Mehalick et al., 2018)
https://forums.phoenixrising.me/thr...-subsets-with-clinical-outcomes-in-cfs.57597/

Decreased Expression of the CD57 Molecule in T Lymphocytes of Patients with Chronic Fatigue Syndrome.(Espinosa, 2019)
https://forums.phoenixrising.me/thr...chronic-fatigue-syndrome-espinosa-2019.77241/

A systematic review of natural killer cells profile and cytotoxic function in ME/CFS (Eaton-Fitch et al. 2019)
https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-019-1202-6

ME/CFS patients exhibit altered T cell metabolism and cytokine associations (Hanson et al. 2020)
https://forums.phoenixrising.me/thr...ytokine-associations-hanson-et-al-2020.79143/

...As well as this oldie-but-goodie:
Comparative Analysis of Lymphocytes in Lymph Nodes and Peripheral Blood of Patients with Chronic Fatigue Syndrome (Fletcher et al., 1999)
https://forums.phoenixrising.me/thr...analysis-of-lymphocytes-in-lymph-nodes.10697/
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I did do some reading into this. While my NHS blood results have never shown anything as being low or high, my lymphocytes definitely have come back low. However lymphocytes is a catch all for all immune cell types, so I don't see how that's helpful as it doesn't give a better proportion of what is low. Is there a good medichecks or UK based test for this? I was struggling to find one that will test for and show the different cell volume numbers. Instead of a number for lymphocytes on there own which seems a bit useless.

1615364693477.png
 

Pyrrhus

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Although most studies that look at lymphocytes in ME tend to look at NK Cells or Cytotoxic T cells, there are some studies that look at B Cell lymphocytes:

Skewing of the B cell receptor repertoire in myalgic encephalomyelitis/chronic fatigue syndrome (Sato et al., 2021)
https://forums.phoenixrising.me/thr...ronic-fatigue-syndrome-sato-et-al-2021.83432/
Sato et al 2021 said:
IGHV3-30 and IGHV3-30-3 genes were more frequent in patients with an obvious infection-related episode at onset, and correlated to expression levels of interferon response genes in plasmablasts. Collectively, these results imply that B cell responses in ME/CFS are directed against an infectious agent
 

godlovesatrier

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Pyrrhus

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...Also note that the sympathetic branch of the autonomic nervous system can suppress immune cells.

In the case of Natural Killer (NK) cells, the autonomic nervous system uses the cortisol (glucocorticoid) and β2 adrenergic (epinephrine) receptors to suppress the activity of NK cells:

1644290055445.png


Also note that Natural Killer (NK) cells appear to be the first line of defense against the re-activation of herpesviruses:
  1. Herpesviruses tend to re-activate in response to pro-inflammatory cytokines.[1]
  2. Exertion is often accompanied by activation of the sympathetic nervous system.
  3. Activation of the sympathetic nervous system decreases the function of NK cells.[2][3]
  4. NK cells are the most potent immune cell for preventing re-activation of herpesviruses, for some reason.[3][4]
  5. So prolonged activation of the sympathetic nervous system by exertion might eventually lead to re-activation of a herpesvirus. One example of this is the outbreak of cold sores that some people experience in response to stressful episodes.

References:
[1] https://pubmed.ncbi.nlm.nih.gov/9475116/
[2] https://content.iospress.com/download/advances-in-neuroimmune-biology/nib006?id=advances-in-neuroimmune-biology/nib006
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144531/
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788305/
 

heapsreal

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While the video explanation in the last link is really very interesting viewing I think it's at odds with other cd4/cd8 research
Interesting video. I dont think its totally at odds with other research. Griffith university in Australia although do alot of research on nk function in mecfs patients, i recall they have done research showing mecfs pts have low cd8 function.
It would be good to try some of those drugs that can increase T cell function😉. It wasnt long ago researchers were denying infections involement in cfs other than the intial onset, but these types of studies are showing its quite possible that these infections that are not an issue for healthy people can be an issue for cfsers, not necessarily the cause but they are playing a role.
👍
 

heapsreal

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So taking hydrocortisone would make NK suppression worse? I can't remember if hydrocortisone is immunosuppressant or not.
Id think its healthy to have cortisol within the normal range. I cant remember the name of the cortisol guru but he wrote the book on 'the safe use of cortisol'. He was there when cortisol was first being used etc. I believe he mentions that ones immune function suffers if cortisol is too low or chronically too high.
Id think if 5-10mg of hydrocortisone helps you get moving and function vs being in the fetal position all day, id take the HC.
 

godlovesatrier

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Yeah Wayne posted possibly the same fella about a doctor who basically thinks it's all cortisol related. But my cortisol has always been fine.

No doubt it's a subset for some or a misdiagnosis.

Yeah absolutely. There are lots of things I'd take if I was more severe.
 

Pyrrhus

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Related discussion:

Dr. Amy Proal interviews Dr. Liisa Selin about T cell exhaustion and viral activity in ME/CFS
https://forums.phoenixrising.me/thr...xhaustion-and-viral-activity-in-me-cfs.86179/
CD8 T-cell exhaustion is a feature of post-viral syndromes like ME/CFS
In order to get CD8 T-cell exhaustion, you have to have a viral antigen that doesn’t clear
Some people become ill after the flu, this may be because their latent viruses reactivate
[...]
Some people who get long-COVID had asymptomatic COVID, this points to the possibility that some people who get ME/CFS may not have been aware of the triggering infection.
 

Pyrrhus

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An interesting comment from another thread:

From the Defining ‘T cell exhaustion’ (Nature, 2019) —
It is important to start off by stating that the term ‘T cell exhaustion’ is a basket term that describes various distinct epigenetic and metabolic states of post-thymic T cells.
The term ‘exhaustion’ is used mainly to refer to effector T cells with a reduced capacity to secrete cytokines and increased expression of inhibitory receptors. These cells were thought to be hypofunctional effector T cells that differentiate from normal effector T cells in response to a chronically high antigen load. However, several observations have challenged this view and suggest that exhausted T cells are heterogeneous, have crucial roles in limiting viral infection or tumour growth and may develop independently from normal effector T cells
When an infection cannot be cleared by the host, a détente can occur whereby pathogen- specific T cells curtail their antipathogen function to avoid causing damage to normal tissues. Importantly, T cell exhaustion does not involve the complete absence of function: exhausted T cells can proliferate in vivo, produce effector molecules, including inflammatory cytokines and granzymes, and exert some control over pathogens or tumours
exhaustion is often seen as a dysfunctional state, it also allows T cells to persist and partially contain chronic infections without causing immunopathology.