Viral Infection Promotes Factor in T-cells Leading to Brain Tissue Destruction

Viral Infection Promotes Factor in T-cells Leading to Brain Tissue Destruction

Infection with lymphocytic choriomeningitis virus triggers expression of a factor called TOX in immune cells strengthening their migration into the brain and promoting damaging effects, including inflammation and tissue destruction.

These findings represent a new piece of the puzzle about the mechanism underlying autoimmune diseases  like multiple sclerosis (MS).

The study “Expression of the DNA-Binding Factor TOX Promotes the Encephalitogenic Potential of Microbe-Induced Autoreactive CD8+ T Cells,” was published in the jounal Immunity.

The bulk of currently available therapies for MS are capable only of managing disease symptoms, without targeting and resolving the disease’s underlying causes.

But the causes of MS, however, are still a mystery. Researchers know that both genetic and environmental factors participate in the disease onset, but why only certain people develop MS is far from clear.

Researchers at the University of Geneva (UNIGE) and Geneva University Hospitals (HUG), Switzerland, decided to investigate the link between infections and MS.

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“We decided to [analyze] the infectious factors by studying the auto-immune reactions provoked by different pathogens,” Doron Merkler, study lead author, said in a press release. Merkler is a professor in the Pathology and Immunology Department in UNIGE’s faculty of medicine and in the HUG Clinical Pathology Department,

“This was to try to pinpoint an element that might influence the development of multiple sclerosis where there has been an infection,” Merkler added.

The team injected two pathogens – a bacteria called Listeria monocytogenes and the lymphocytic choriomeningitis virus – in healthy mice and looked at the animal’s immune responses, analyzing specifically a pool of immune cells called CD8 T-cells.

“We saw a quantitatively identical immune reaction from the lymphocytes called CD8+ T,” said Nicolas Page, study’s first author and a researcher at UNIGE’s. “However, only the mouse infected with the viral pathogen developed an inflammatory brain disease reminiscent to multiple sclerosis.”

They then looked deeper into the genes of the CD8 T-cells and how each pathogen influenced their activation.

Researchers found that TOX, a DNA-binding factor, was only activated during the lymphocytic choriomeningitis virus infection. Moreover, TOX activation was essential for inflammation in the brain.

“We found that the inflammation environment influences the expression of TOX in T lymphocytes, and that it could play a role in triggering the illness,” said Page.

The team then transferred CD8 T-cells depleted of TOX into a mouse model of brain inflammation that  had been infected with the viral pathogen. Although the animals received the virus, researchers saw they failed to develop MS-like symptoms.

The researchers suggest that TOX alters the expression of receptors at the surface of CD8 T-cells that prevent these cells from migrating into the central nervous system, inducing damage.

When analyzing human MS lesions, researchers also found infiltrating T-cells expressing TOX.

“This is an encouraging result for understanding the causes of the disease but there is still lots of work to be done to ascertain what really causes multiple sclerosis in humans,” said Page.

The team plans to further investigate the activity of Tox and its involvement in auto-immune diseases.

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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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    • Susan Eaton says:

      I was taught environment was was the when, where, what, and how’s of the external factors possibly effected one from the environment in which a person was raised.”
      . These are things like growing up in a rural area where fields of crops surrounded you. Especially back when harsher insecticide chemicals were sprayed. Or in areas where wells were the main water source. Other factors, such as city traffic, smog, noise exposure as in large cities. A 24/7 lifestyle, working in a casino as compared to a postal delivery person who works a regular morning in a quiet suburban area. Whether, as a child, you experience abuse or a scene of not being nurtured. Major stress levels
      are frequently associated with physical decline of health. Such as, a major career change, loosing a loved one, moving, marriage or divorce.
      Environmental effects can and do cause emotional and psychological pressures. If those pressures are extreme, last long periods of time, or are permanent, they to effect ones heath, but as far as I know, from 19 years of reading about psychological and emotional conditions as pertained to MS, the only correlation I have discovered is that stress and other psychological pressures are draining and on occasion, cause one to become more susceptible to sickness, such as cold or viruses, but there has not been any research of any type that has proved anything “caused” MS. I believe, as states in this article, all of these type things are part of a puzzle. But to specifically address you question, emotional and psychological state are not included in environmental factors. Emotional and psychological state would more likely be a result of environmental factors and/or perhaps genetics.

      • WADALBERTB'S says:

        13/01/2018 · by wadalbertb – on the internet at www wadalbertb’s
        Unfortunately, the entire text is in Polish, so not much available for English speakers but it is worth reading, because there are express suggestions about the causes of MS. So chickenpox and shingles can be the catalysts of multiple sclerosis. Psychology, psychology undoubtedly favors the development of the disease, and I learned during this time, lowering my immunity. It favored the development of MS
        I fully appreciate your suggestions and I recommend adding mys. Maybe researchers will take this into account.

      • Donnia says:

        Hmmm.. your comments, describe me.. lived on a farm, worked in fields from age 9 to 16.. delivered mail, walking routes, for 19 years.. till I was diagnosed – plus 2 neck surgeries later – disability retirement from the postal service.. now more and more MS symptoms.. I am 48.

  1. Kate Harris says:

    Well it’s a silly infection probably MAP Bacteria or Chlymidia, but whatever it is they should hurry up and fix it because we are all suffering and even dying out here! The Standard treatment for MS is just SO pityfully LAME it is very lamantable!
    This morning I awoke to jumping vision and a horrible buzzy type feeling in my head and left leg with NO HELP FOR IT AT ALL! Bamboo shoots stuck up the finger nails as a form of TORTURE would be more tolerable than this!

  2. Matthew Coil says:

    Kate Harris thank you for your passion. We are all suffering at varying degrees of progression and the MS treatment industry seems to get hung-up on treatments that have worked in some instances so it should work in every case but we know that it is just not that simple. I worry that the clinic where i get Tysabri sees my treatments as a steady cash flow so they may not benefit if i change my treatments. the Clinic may not be motivated to see new treatments and solutions come along. Does anyone else feel this same way?

    • Graham Betts says:

      I do absolutely it seems to be the big dollar that drug companies make from insurances but medicine must get more advanced and research the true cause of MS and prevent it!

    • Susan Eaton says:

      The scientific community, and specifically MS researchers, do know that MS treatment drugs only lesson the number of relapses. Or maybe I should sayid the treatment works, it works to increase the length of time between relapses. From what I have read, to date, the treatments only work i. About 50% of person with MS. It is my understanding that there is no cure and no known cause. The best one can possibly do is to maintain a close relationship with a doctor who is able and willing to treat symptoms as they occur. I take not medicine specifically labeled for MS treatment, but I am prescribed a variety of medication and supplements, by my Internal Medicine doctor to combat and relieve ever changing (sometimes on a daily basis) symptoms of fatigue, pain, numbness, tingling, destorted vision, blurred vision, vertical diplopea, emotional and cognitive changes, BP, anxiety, ….. and the list goes on.

  3. NOREEN says:

    Interesting article, but alas it doesn’t solve the problem just more possible answers. I personally believe that perhaps we all have the possibility of having MS, something needs to trigger it. 19 years ago my life was unbelievably stressful, then my 6 week old son was taken into intensive care unit with RSV and bronchiolitis. I remained with him in an isolation room – after 1 week we returned home the next morning i woke up with one eye completely fogged over. Retrobulbar neuritis – the beginning of my journey into MS. Viral+Stress = MS?

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