T cell research

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T cell research

Postby bromley » Wed Dec 27, 2006 2:30 pm

T For Two: Scientists Show How Immune System Chooses Best Way To Fight Infection 27 December 2006

A new study has suggested a novel way of combating diseases related to the immune system, including cancer and autoimmune diseases such as type I diabetes and arthritis. The study, funded by the Wellcome Trust, appears online in the journal Nature.

T cells are produced by the body to fight infection. Scientists previously identified two types of T cell, both produced in the thymus: "effector T cells", which attack infected cells, and "regulatory T cells", which suppress the immune system, protecting the body from inflammatory damage during infection. Regulatory T cells, if given to individuals receiving transplants, may help suppress the rejection response.

Now, a team of researchers has discovered a novel mechanism determining whether a maturing T cell is likely to emerge from the thymus as an effector cell or a regulatory cell. The research suggests that new treatments could be developed to deliberately affect the type of T cells produced, allowing scientists to tackle a number of diseases which are influenced by these different types of T cells.

"Our team has shown that a process known as 'trans-conditioning', which we knew to be involved in T cell development, actually has a profound influence on whether a T cell becomes an effector or a regulatory cell," explains Professor Adrian Hayday of King's College London. "This may be clinically significant; if we can find a way to influence this process, it may be possible to make the body produce effector T cells in a cancer patient or regulatory T cells in someone suffering from autoimmune disease, both of which are caused by the immune system malfunctioning."

Professor Hayday and his team believe that the findings may also answer one of medical research's mysteries: why autoimmune diseases in women commonly go into remission in pregnancy.

"We believe that trans-conditioning is less active during pregnancy," says Professor Hayday. "This means that most T cells emerging at that time will be regulatory. Regulatory T cells prevent an over-active immune system from causing inflammatory damage to the body. This may be one of the key steps in preventing the mother from rejecting the foetus growing inside her."

The research was carried out at the King's College London School of Medicine at Guy's Hospital and was co-lead by Dr Daniel Pennington, a Wellcome Trust VIP awardee and now at Queen Mary, University of London. Collaborating researchers were based at Faculdade de Medicina de Lisboa, Lisbon; University College, London; Yale University School of Medicine; Institute for Animal Health; and Imperial College London.

Source: ScienceDaily Copyright © 1995-2006 ScienceDaily LLC
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Postby Chris55 » Wed Dec 27, 2006 4:43 pm

I only have one (BIG) problem with the autoimmune/T-cell theory. The MS drugs that suppress the immune system may or may not reduce relapses. However, disability seems to continue in spite of immune suppression.

If there is an infection that the immune system is trying to fight, suppressing the immune system might be just the wrong thing to do.

Think of the syphillis(sp?) bacteria. It leaves the blood stream, migrates to the brain where is attacks for 15-20 years with no evidence of infection. Without treatment, by the time it is detected, it is too late.

Just some thoughts...
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Postby Lyon » Wed Dec 27, 2006 9:03 pm

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Postby Chris55 » Thu Dec 28, 2006 12:04 pm

Lyon--to be more specific, articles I have read seem to indicate that the CRABs only have an effect on relapses--not disability. And again, how does one measure drug effectiveness with MS? In other words, suppose one takes a CRAB drug for 10 years and only has a few relapses. Then the disease kind of takes off. That could very well be the course of the disease WITHOUT taking a CRAB drug.

A doctor presented not long ago showing the MRIs of 2 patients. One had lots of lesions but no relapses. The other had no lesions and lots of relapses. ???

There is still SO much we do not know. My personal opinion at this point is the immune attack is a "by-product"--not a cause. Still not convinced the T cells are the problem. Autopsies were done on 2 MS patients who died while in the middle of a relapse. Their brains were actually studied. What they found were dead/dying myelin-producing cells AND they were NOT killed by T cells. That pretty much shoots the autoimmune theory out the window for me.

Like you, I just wish they could spread the research around instead of sealing the autoimmune theory in a box and covering it with shipping tape! To me, it is like the oil companies. The instant someone invents a cost-efficient automobile, one of the oil companies buys the inventor out. The same is true with MS research. When a potentially effective new med was found (Minocycline), it was sucked up by Copaxone.


We have to face the fact that MS research/medication right now is being totally controlled by the current CRAB drug companies.

When I learned Copaxone was conducting one of the biggest--and most expensive--drug trials to determine the anitbody rates of its competitors--well, I simply wanted to scream and then cut my throat! For me, that has been one of the biggest insults to MS sufferers and their loved ones!
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Postby HarryZ » Thu Dec 28, 2006 12:51 pm

Chris,

I'm afraid that I am going to have to agree with every point that you made in your last message :)

The amount of money being spent by the "big four" MS drug companies to ensure that their product keeps and/or increases its share of this very lucrative market, is huge.

I have a feeling that if you were to privately ask every major MS researcher who wasn't being paid as a spokesperson for the CRAB pharmas, they would tell you that the CRABs aren't worth the price of admission and have been more than a disappointment in their efficacy.

But they continue to bring in immense amounts of revenue for these companies and will be kept front and center for as long as they can.

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Postby Chris55 » Thu Dec 28, 2006 4:32 pm

Touche' my friend! Harry, when I first read your post I thought it said you "disagreed" with everything I said--LOL!

I guess the biggest problem I have is that I am not stupid! (Not directed at anyone on this board or elsewhere! Quite the contrary, I find posters on this site to be extremely bright!) I can read--and understand--research results. I have no problem seeing the forest for the trees!

I think the CRAB drugs outlived their usefulness a long time ago. I get a kick out of reading their trial results--for me, totally manipulated and totally unproveable because there is NOTHING consistent with this disease from person to person. Everytime my daughter had a non-typical MS symptom--poof! it became a new MS symptom! (Or more insulting, "in her head".)

That is also one of my biggest complaints about MS treatment. Every time she called her MS specialist--no matter her complaint/comment--they just threw a new drug at her or increased ones she was already on. By the time she tried her current alternative treatment, she was so drugged up she was like a Zombie. As she said, 'I felt like I was zipped up in a body bag".

I have no solution for the CRAB drug monopoly but as many of you already know, I definitely support alternative treatments as long as they do no harm!

I simply refuse to give up, damn-it! Bless all of you--each and every one! My heart is truly yours--Chris
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Postby Lyon » Thu Dec 28, 2006 4:34 pm

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Postby HarryZ » Thu Dec 28, 2006 7:27 pm

Chris,

Chris55 wrote:Touche' my friend! Harry, when I first read your post I thought it said you "disagreed" with everything I said--LOL!


That's why I placed that little "smile" at the end of the sentence :)

I think the CRAB drugs outlived their usefulness a long time ago. I get a kick out of reading their trial results--for me, totally manipulated and totally unproveable because there is NOTHING consistent with this disease from person to person. Everytime my daughter had a non-typical MS symptom--poof! it became a new MS symptom! (Or more insulting, "in her head".)


The CRABs first started to appear in 1991 and here we are 15 years later and the price of them continues to go up!! Charge as much as you can to keep the bottom line very black!!! 3 of the 4 were given Orphan Drug Status and that has made them even more money.

Back in 1996 my wife's MS neuro told her the ABC's at the time wouldn't do her much if any good....suggested two good holidays a year would do her far better! Then in 2000, he told her that the MS docs were very disappointed in the ABC's and that they weren't doing what they thought they would do. He only said this to her because she was a nurse, and had been going to the clinic for years. He would never make such a statement publicly.

I have no solution for the CRAB drug monopoly but as many of you already know, I definitely support alternative treatments as long as they do no harm!


My wife has been using Prokarin successfully for 6 1/2 years now. While it likely won't stop the progression of the disease over time, it certainly has improved many of her symptoms to a large degree, especially the fatigue.

Harry
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More T-Cell Info

Postby Shayk » Thu Dec 28, 2006 9:33 pm

Lyon

You wrote:
There's lots of room on this site for a variety of opinions though!

You seem to know a lot about auto-immune stuff and T cells (I certainly don't), so I'm curious to know what you think about the concept of "beneficial auto-immunity" and this abstract.
An investigation of auto-reactivity after head injury
Murine models of CNS injury show auto-reactive T cell responses directed at myelin antigens, associated with improved neuronal survival and functional recovery. This pilot study shows, for the first time, that similar immune responses against myelin occur in human traumatic brain injury (TBI), with an expansion of lymphocytes recognising myelin basic protein observed in 40% of patients studied. "Reactive" patients did not have greater contusion volume on imaging, but were younger than the "unreactive" subgroup and tended towards a more favorable outcome. These findings are consistent with the concept of "beneficial autoimmunity".

Obviously this is not MS research but I find the idea of "beneficial autoimmunity" an interesting one. Do you think beneficial auto-immunity is a possibility (based on what you know about auto-immune T cell stuff)?

Sharon
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Re: T cell research

Postby NHE » Fri Dec 29, 2006 3:22 am

Chris55 wrote:Autopsies were done on 2 MS patients who died while in the middle of a relapse. Their brains were actually studied. What they found were dead/dying myelin-producing cells AND they were NOT killed by T cells. That pretty much shoots the autoimmune theory out the window for me.

I'm not trying to argue one way or the other, but a sample size of 2 is hardly conclusive. At most, that study represents interesting data that will hopefully lead to further investigations.

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Re: T cell research

Postby Lyon » Fri Dec 29, 2006 8:07 am

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Re: T cell research

Postby HarryZ » Fri Dec 29, 2006 8:16 am

I'm not trying to argue one way or the other, but a sample size of 2 is hardly conclusive. At most, that study represents interesting data that will hopefully lead to further investigations.

NHE


Examining only 2 samples would, under normal circumstances, not mean too much. But add to that the work by Drs. Prineas and Barrett on the autopsy they did within 24 hours on the young 17 year old lady who died from a massive MS exacerbation. No immune system activity was evident in that case. They also went on to more carefully examine 12 other MS brain samples they had and found 7 others where the auto immune system showed no presence in the severe lesion activity.

Now we have a number of situations where very damaging demyelination has taken place but the immune system isn't even aware of the problem! So what is causing this massive damage? As usual with MS, there always seems to be more unanswerable questions but at least the scientists are beginning to learn that more work is required other than remaining on the "auto-immune theory" which has produced next to nothing in the effective treatment of MS.

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Re: T cell research

Postby Lyon » Fri Dec 29, 2006 8:35 am

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Re: More T-Cell Info

Postby Lyon » Fri Dec 29, 2006 8:45 am

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Numbers in research--one is enough sometimes

Postby lyndacarol » Fri Dec 29, 2006 9:42 am

This posting has nothing to do with T-cells, but rather with research, in general. This seems to be under discussion here, so let me just add my thought:

Dr. Douglas Feinstein (at U of Illinois-Chicago) learned of one woman with MS who improved when she took pioglitazone (Actos), a drug used for diabetes. It is my understanding that a larger study with the drug and MS is ongoing now.

I have heard of other studies conducted after very few people responded to something. I think one or two should be enough to warrant investigation, if one can only find an interested researcher with the funding. (Difficult since drug companies are sponsoring most, I think, and only want work that would benefit their products)

As you can probably guess, I think Prineas and Barnett are on to something. I don't believe MS is initiated by the immune system. Count me with the many in the "Not-Autoimmune Camp" and as the singleton in the "Excess-Insulin Camp." (I don't mind being that lone advocate among kind friends here who hold many differing opinions.) The key to this dreadful disease is out there in some box. We have a better chance of finding it if we are not all looking in the same box!
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