Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/mya

[Allyann]

NCNED announced today their latest scientific paper that has been accepted for publication
http://www.ncbi.nlm.nih.gov/pubmed/27001659

 

[IrisRV]

And now, a translation.... someone? Anyone? Please? I don't speak immunology beyond the very basics.

 

[Remy]

It basically just says that MECFS patients have increased numbers of Treg cells...which is interesting. And higher levels of these positive iNKT cells (and I have no idea what those are honestly though their name suggests they are made by Apple. ) and lower levels of the negative variety.

But it's basically just identifying some common differences and then suggesting further research. It seems like an awfully small sample to be making generalizations though...

Asian Pac J Allergy Immunol. 2016 Mar 20. doi: 10.12932/AP0733. [Epub ahead of print]
Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison.

Ramos S1, Brenu E, Broadley S, Kwiatek R, Ng J, Nguyen T, Freeman S, Staines D, Marshall-Gradisnik S.
Abstract

BACKGROUND:

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), and Multiple Sclerosis (MS) may share some similarities in relation to reduced NK cell activity. It is likely that other cells such as regulatory T (Tregs), invariant Natural Killer T (iNKT) and gamma delta T (γδ T) cells may also be dysregulated in CFS/ME and MS.
OBJECTIVES:

To evaluate and compare specific immune regulatory cells of patients with CFS/ME, patients with MS and healthy controls.
METHODS:

Sixty three volunteers were included in this study, 24 were CFS/ME patients, 11 MS patients and 27 healthy controls. Blood samples were obtained from all the participants for flow cytometer analysis of iNKT cell, Tregs and γδ T cell phenotypes.
RESULTS:

We observed significant increase in Tregs in the CFS/ME group (p≤0.005) compared with the healthy controls group. Total γδ and γδ 2 T cells were significantly reduced in the MS patients in comparison with the healthy controls group. Conversely, CD4+iNKT percentage of iNKT, was significantly increased in the CFS/ME group compared with healthy controls and double negative iNKT percentage of iNKT significantly decreased compared with the healthy controls group.
CONCLUSION:

This study has not identified immunological disturbances that are common in both MS and CFS/ME patients. However differential expression of cell types between the conditions investigated suggests different pathways of disease. These differences need to be explored in further studies.

 

[Seanko]

From Bite Sized Immunology

Regulatory T cells
As the name suggests regulatory T cells (also called Tregs) are T cells which have a role in regulating or suppressing other cells in the immune system. Tregs control the immune response to self and foreign particles (antigens) and help prevent autoimmune disease.

Invariant NK Cells

Invariant natural killer T (iNKT) cells, also known as type I or classical NKT cells, are a distinct population of T cells that express an invariant aβ T-cell receptor (TCR) and a number of cell surface molecules in common with natural killer (NK) cells. Although iNKT cells are rare in the human blood pool, comprising just 0.01-1% of peripheral blood mononuclear cells (PBMCs), they are important immunoregulatory cells rapidly producing large amounts of cytokines that can influence other immune cells.

Gamma Delta T cells

Gamma delta (gd) T cells are the prototype of ‘unconventional’ T cells and represent a relatively small subset of T cells defined by their expression of heterodimeric T-cell receptors (TCRs) composed of g and d chains. This sets them apart from the classical and much better known CD4+ helper T cells and CD8+ cytotoxic T cells that are defined by ab TCRs. Like these cells they are mostly thymus dependent.

 

[Remy]

Testing these Tregs seems to be a bit challenging. I thought it was just a matter of testing CD25+CD4+ cells but I was told that you have to only measure a subset of those cells that display this Foxp3+ marker too.

I would have bet Tregs would be low in MECFS. But who knows exactly what subset they measured in this study. It's all a little Greek to me.

Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease.
Review article
Sakaguchi S, et al. Immunol Rev. 2006.
Show full citation
Abstract
Naturally arising CD25+ CD4+ regulatory T (Treg) cells, most of which are produced by the normal thymus as a functionally mature T-cell subpopulation, play key roles in the maintenance of immunologic self-tolerance and negative control of a variety of physiological and pathological immune responses. Natural Tregs specifically express Foxp3, a transcription factor that plays a critical role in their development and function. Complete depletion of Foxp3-expressing natural Tregs, whether they are CD25+ or CD25-, activates even weak or rare self-reactive T-cell clones, inducing severe and widespread autoimmune/inflammatory diseases. Natural Tregs are highly dependent on exogenously provided interleukin (IL)-2 for their survival in the periphery. In addition to Foxp3 and IL-2/IL-2 receptor, deficiency or functional alteration of other molecules, expressed by T cells or non-T cells, may affect the development/function of Tregs or self-reactive T cells, or both, and consequently tip the peripheral balance between the two populations toward autoimmunity. Elucidation of the molecular and cellular basis of this Treg-mediated active maintenance of self-tolerance will facilitate both our understanding of the pathogenetic mechanism of autoimmune disease and the development of novel methods of autoimmune disease prevention and treatment via enhancing and re-establishing Treg-mediated dominant control over self-reactive T cells.

 

[Seven]

name suggests they are made by Apple. )

You made my day.

 

[Seanko]

And now, a translation.... someone? Anyone? Please? I don't speak immunology beyond the very basics.

I do like people's honesty on this forum.

On another one, somebody posted an incomprehensible abstract & various individuals pretended to understand. I remarked that that this was unlikely...I was of course censored

 

[Strike me lucky]

So my understanding is that ME is much more severe than MS so should get funding greater than MS

 

[Tony L]

Good and bad news I guess. Bad news is that this adds to the weight of research pointing to a seriously dysfunctional immune system but good in that it is highlighting the fact that we are sick in body and need appropriate care and support from our health services.

Consistent with other published work comparing ME with MS. Both diseases involve abnormal immune function but significantly different presentations.

 

[Baz493]

The elevated Treg levels mentioned in this thread, as relating to ME, also seem to be implicated in long covid. People with long covid have been found to have over double the normal levels of Treg cells. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10059134/ In trying to understand my own cadmium induced long term health issues I was able to learn that it involved a complicated series of biological events, some of which seem to be involved in the long covid levels of Tregs. Cadmium upregulates synthesis and degradation of retinoic acid through the gene's affecting them. Among many other factors involved this directly affects Treg levels. https://www.nature.com/articles/s41423-022-00869-y People with severe covid experience low vitamin A levels, consistent with conversion of the vitamin to retinoic acid to try to both fuel immune response and Treg regulation of that response. Once that regulation becomes out of control the patient with covid tended to either experience severe covid or longer term responses. Although retinoic acid dysregulation is unlikely to explain everything about ME I am guessing that it is a significant piece of the puzzle.