This Is MS Multiple Sclerosis Community: Knowledge & Support

The article in the previous posts explains a lot about T-Cells and I think I will summarize it as follows:

1. It appears that MS is a T-cell mediated disease. In particular, helper T-cells otherwise known as Th cells (specifically the pro inflamitory helper T-cells Th1 and Th17).

2. Helper T-cells do not directly interact with tissues, but they recruit other cells such as macrophages and neutrophils to perform the actual cell destruction found in MS lesions via cytokines (chemical signals).

This is why T-cells are found surrounding the lesion at its surface but are rarely found within the lesion (in contrasts macrophages and neutrophils are found in the lesion).

3. It appears that helper t-cells are self reactive when they are developed in the thymus because they are not exposed to all auto-antigens during development. This is true of healthy individuals also.

4. It is the job of regulatory T-cells (Tregs) to prevent these helper T-cells from initiating a response against tissues in the central nervous system.

5. It seems that regulatory T-cells in people with MS are defective in providing this protection.

Here is another article that explains this in more detail:

http://www.sciencedirect.com/science/ar ... 1410000043

6. It seems that there is another variant of regulatory T-cells that can be developed that are separate from the naturally occurring regulatory T-cells which can prevent an auto-immune response by helper T-cells. These are known as induced or adaptive regulatory T-cells (iTreg, aTreg).

7. There is mounting evidence that Vitamin D (a steroid hormone) appears to promote the development of regulatory T-cell function.

African-Americans who have multiple sclerosis (MS) have lower vitamin D levels than African-Americans who don't have the disease, according to a study published in the May 24, 2011, print issue of Neurology®, the medical journal of the American Academy of Neurology. However, most of the difference in vitamin D levels was due to differences in climate and geography.

"MS is not as common in African-Americans as it is in whites, although the disease tends to be more severe in African-Americans," said study author Ari J. Green, MD, of the University of California San Francisco and a member of the American Academy of Neurology. "We have known that vitamin D levels are associated with MS and that African-Americans are at increased risk for having low vitamin D levels, but little research has been done to look at vitamin D levels in African-Americans with MS."... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1334

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It appears that there is a lot of research now being conducted on regulatory T cells in areas where self tolerance is defficient (autoimmune diseases and allergy) as well as when tolerance needs to be induced (transplant rejection).

Here is a recent Podcast with Professor Robert Lechler, King's College London who is working on regulatory T-cells therapies to prevent transplant rejection, but also describes how these cells are crucial in the prevention of autoimmune diseases such as MS and Rheumatoid Arthritis:

http://nakeddiscovery.com/downloads/split_individual/11.05.22/Naked_Scientists_Show_11.05.22_8516.mp3

Here is an article that was published in Scientific America about regulatory T-cells. It describes how they are believed to control many different autoimmune diseases:

http://www.smccd.net/accounts/digennaroc/biology430/Articles/Regulatory_T-cells.pdf

Here is a review article about regulatory T-cells and their function in autoimune diseases from The New England Journal of Medicine:

http://www.oncoinmun.cl/pdf2008/ihq2008/1166.pdf

As shown in this thread, many researchers investigating autoimmune diseases are finding that the Treg function of people with these diseases are defective.

Here is another paper by researchers investigating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) which is a disease similar to MS that effects the meylin sheath in the periphery (not the CNS).

http://www.ncbi.nlm.nih.gov/pubmed/19886739

Conclusion is that Tregs are defective in people with CIDP compared with healthy controls.

To explain a little more about vitamin D and its connection to regulatory T cells, I would first like to summarize some facts about Vitamin D.

1. Vitamin D is not a vitamin. It is a steroid hormone. You cannot get natural amounts of vitamin D from foods. For example, a healthy person in mid-day summer sun can synthesis 10,000 IU's of vitamin D in 1 hour. Compare this to the amount that is fortified in a glass of milk which is about 200 IU's.

2. There are three stages to vitamin D synthesis in the body. The first is called Cholecalciferol which is generated by UV exposure. This is the same as Vitamin D3 that you can purchase at any drug store.

Cholecalciferol is then hydroxylated in the liver to become calcifediol (25-hydroxyvitamin D3, otherwise known as Calcidiol). This is the main circulating form in your blood and is what should be checked by your doctor.

Finally, calcifediol is again hydroxylated, this time in the kidney but also by immune cells, and becomes calcitriol (1,25-dihydroxyvitamin D3). Calcitriol is the most active hormone form of vitamin D3.


3. There is mounting evidence that Vitamin D3 has a direct effect on regulatory T-cells. These Treg-cells restrain the immune system to prevent autoimune diseases and maintain self tolerance.

It appears from the mounting evidence that Tregs are defective in their supressive function in people with MS as well as other autoimune diseases.

I believe this is why there is such great success with the HSCT procedure, because it wipes out these defective Tregs and enables normal Tregs to perform their proper function in people with auto-immune diseases.

The key thing to remember is that all people generate self-reactive immune cells, but it appears that people with autoimmune diseases lack the function to shut-down an autoimmune response because of the lack of suppressing ability of their Tregs.

Here is a recent article that describes this:

http://www.ima.org.il/imaj/ar10mar-11.pdf

So to me, it is a no brainer to follow the recent studies of high doses of vitamin D (Phase I/II) on people with MS. I cannot understand why the MS community is not pushing for more research on vitamin D to find the optimum levels. There has been suspicion of a connection of vitamin D's role in preventing MS for more than 30 years, but little has been done to investigate this.

Here's some more info on Vitamin D3.

Relapse frequency has been found to correlate inversely with vitamin D3 levels. 50-60 ng/mL (125-150 nmol/L) is a good target range. Note, the conversion factor for 25(OH) vitamin D3 ng/mL -> nmol/L = 2.496

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NHE

you might also enjoy this:

http://www.thisisms.com/ftopicp-129213.html#129213

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my approach: no meds so far - just balanced whole foods (partial 'paleo', much less outright elimination), science, supplements, & bloodwork
my regimen - www.thisisms.com/ftopict-2489.html
www.whfoods.com, www.nutritiondata.com

I don't know why there is such an unwillingness to investigate vitamin D. It seems that the only work being done is by NIH grants on the basic science and a few initial trials from researchers outside of the U.S.

I think the National MS Society has really dropped the ball here. When I first got sick and found out that MS has a latitude gradient and this may be due to sunlight exposure and vitamin D levels, I had to ask myself why isn't this being researched more fully?

It would be a shame if the cure for MS (and many other autoimune diseases) is simply a matter of having the right level of serum 25OHD3. Something that could be taken care of from supplementation that is readily available at any drug store.

Personally, I think there is a revolution waiting to happen in healthcare and Vitamin D is the key.

Here is a good organization that also feels the same way:

http://www.vitamindcouncil.org/

Continuing on with the theory that regulatory Tcells (Tregs) provide a protective role against self reactive immune cells in many types of diseases here is a very recent paper that describes the state of Tregs in ALS or more commonly known as Lou Gehrig's disease.

http://brain.oxfordjournals.org/content/134/5/1293.abstract

"These observations were extended into the amyotrophic lateral sclerosis patient population where patients with more rapidly progressing disease had decreased numbers of regulatory T lymphocytes; the numbers of regulatory T lymphocytes were inversely correlated with disease progression rates. These data suggest a cellular mechanism whereby endogenous regulatory T lymphocytes are immunocompetent and actively contribute to neuroprotection through their interactions with microglia. Furthermore, these data suggest that immunotherapeutic interventions must begin early in the pathogenic process since immune dysfunction occurs at later stages."

So, it appears that Treg dysfunction and/or population reduction is key to many diseases outside of MS.

More information about regulatory T-cells as modulators of diseases besides MS, here is a paper that investigates Treg function in a mouse model of HIV-1 Enchephalitis:

http://www.ncbi.nlm.nih.gov/pubmed/20846730



In my view it appears the key is not the fact that immune cells target the bodies own tissue, it is the fact that the regulatory T cells (Tregs) are failing to shut-down the attack on the self.

It looks like there is a revolution happening in health science at this moment with the discovery of regulatory T-cells and diseases and self tolerance.

Here is a good video discussion Tregs and their application in transplant rejection as well as their role in autoimune diseases.

http://www.youtube.com/watch?v=PYHvVj2qaDE

And here is a video discussion regarding Tregs and Parkinsons disease:

http://www.youtube.com/watch?v=2ZJL5pAGTZo

It looks like Tregs will be the basis for future therapies in preventing many types of disease as well as transplant rejection.

Here is a new paper on vitamin D and MS:

http://www.ncbi.nlm.nih.gov/pubmed/21723567



And again, more evidence that Vitamin D promotes Treg cell function/population.

Here's a good review paper on vitamin D. The full paper is free. It discusses many aspects of the activity of vitamin D so don't be dissuaded by the abstract.

http://www.ncbi.nlm.nih.gov/pubmed/15951480


NHE