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Mulltiple Regulatory Cell Types Can't Keep Self-destructive Immune Cells Under Control 15 November 2006

Multiple sclerosis (MS) is an autoimmune disease that occurs when cells of the immune system attack nerves in the brain. Although it is not clear exactly why this self destruction is able to occur, it has been shown that other immune cells that normally keep the destructive ones in check (known as regulatory T cells) are impaired in individuals with MS.

Previous studies have focused on a regulatory T cell subset known as the CD4+CD25 high regulatory T cell subset, but in a study which appeared online on November 9, in advance of publication in the December print issue of the Journal of Clinical Investigation, researchers from Harvard University, now show that IL-10 producing regulatory T cells (Tr1 cells) are also impaired in individuals with MS.

David Hafler and colleagues showed that T cells from patients with MS produced substantially less IL-10 when stimulated ex vivo with antibodies specific for CD3 and CD46 than T cells from healthy individuals. This inability to induce a Tr1 cell phenotype was associated with altered expression of CD46 cytoplasmic isoforms upon activation. This study shows that a second regulatory T cell population (the Tr1 cells) is impaired in individuals with MS and the authors speculate that, as for the CD4+CD25high regulatory T cell subset, this defect is likely to be observed in patients with other autoimmune diseases, such as rheumatoid arthritis.

TITLE: Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis

AUTHOR CONTACT:

David A. Hafler
Brigham and Women's Hospital and Harvard Medical School, Boston,
Massachusetts, USA.

Anne L. Astier
Brigham and Women's Hospital and Harvard Medical School, Boston,
Massachusetts, USA.

JCI table of contents: November 9, 2006

Source: Medical News Today © 2006 MediLexicon International Ltd

This get's back to my posts 101 and 102. It's entirely possible that MS is not so much about an immune system that's stepped up, rather about an immune system whose normal restaints don't work. I wish there was a good way to paint the big picture perspective here. napay

oo

I've not read a lot about Blood Brain Barrier, mainly because it's not implicated so much in MS as part of the activity of the illness, rather it's presented as part of the playing field, not one of the players.

I agree that more understanding is needed.

I recall from my reading that the ability to permeate the BBB is about size of the thing that wants to get through. There's some info regarding ascorbic acid along these lines. There are also, aparently, more than one way in and this is also a complicating factor. Apparently there is a line of understanding that says that it's normal to have white blood cells in the brain.

The best way I think to learn more is to follow up on the various studies for other issues whereby getting a drug through the BBB is being studied. napay

oo

I agree. Nothing about this is easy. I respect your desire to research this. If you've read my 101 and 102 posts, you know I didn't just tap those out overnight. All I can say is .... dig.

You can also learn about this by trying to learn more about the mechanism by which Tysabri and Avonex is theoretically supposed to work. The journal of immunology has a cool search engine I really like.

One thing I will say is that my researching on the various aspects of MS has lead me to have a much greater respect for the science folks, nothing about this is easy and easily pinpointed.

one last thing you might find useful, albeit difficult to watch - there is a film clip on the opexa website that describes some of the theory about the pathogenesis of MS. napay

oo

Lyon,
I found what I believe is the BBB article I keep remembering that I think might be relevant. I put it in a relevant thread at BBB Thread Let me know if you've read this one.
napay