Decreased T cell reactivity to Epstein–Barr virus

[heapsreal]

Objective: To investigate T cell and antibody immunity to Epstein–Barr virus (EBV) in multiple sclerosis (MS).

Methods: Immunoglobulin G (IgG) immunity to EBV nuclear antigen 1 (EBNA1) and viral capsid antigen was measured by enzyme linked immunosorbent assays, and T cell immunity was assessed using enzyme linked immunospot assays to measure the frequency of peripheral blood mononuclear cells (PBMC) producing interferon γ in response to autologous EBV infected B cell lymphoblastoid cell lines (LCL) in 34 EBV seropositive healthy subjects and 34 EBV seropositive patients with MS who had not received immunomodulatory therapy in the previous 3 months.

Results: Patients with MS had increased levels of anti-EBNA1 IgG but a decreased frequency of LCL specific T cells compared with healthy subjects. Using purified populations of CD4+ T cells and CD8+ T cells, we showed that the LCL specific response resides predominantly in the CD8+ population, with a frequency 5–7-fold higher than in the CD4+ population. The decreased CD8+ T cell response to LCL in MS was not caused by decreased HLA class I expression by LCL, and LCL from MS patients could be killed normally by HLA matched EBV specific cytotoxic CD8+ T cell clones from healthy subjects. Furthermore, the decreased CD8+ T cell immunity to EBV was not due to a primary defect in the function of CD8+ T cells because EBV specific cytotoxic CD8+ T cell lines could be generated normally from the PBMC of patients with MS.

Conclusion: This quantitative deficiency in CD8+ T cell immunity to EBV might be responsible for the accumulation of EBV infected B cells in the brains of patients with MS.

http://jnnp.bmj.com/content/80/5/498

The above research was what has lead to the treatment of a previous link i have posted which involved taking the patients T-cells and growing them with an ebv vaccine and reinfusing this back into the patient.

Following the treatment, Gary experienced a significant reduction in fatigue and painful spasms, an improvement in thinking, memory, attention and hand function, and increased productivity at work. There was also reduced disease activity on his MRI brain scan. At the latest follow-up Gary also had improvement in leg movement.

http://www.msaustralia.org.au/news/queensland-researchers-make-major-breakthrough-ms-treatment

 

[heapsreal]

Is EBV really that benign?? Are they really able to test accurately how active this infection is currently??

The above researchers i think are questioning this and finding ebv possibly being an important factor??

 

[heapsreal]

Evidence implicating Epstein–Barr virus (EBV) in the pathogenesis of multiple sclerosis has been increasing over the last 30 years, and this issue of Brain contains an article and correspondence addressing the issue of EBV infection in the brains of people with multiple sclerosis. To appreciate how EBV might contribute to the development of multiple sclerosis, it is necessary to understand some key aspects of EBV infection.

EBV is a human herpesvirus with the unique ability to infect, activate and persist in latent form in B lymphocytes for the duration of the infected individual’s lifetime. The virus infects naïve B cells, driving them out of the resting state into proliferating lymphoblasts and exploiting the normal pathways of B cell differentiation so that the B blasts become memory cells (Thorley-Lawson and Gross, 2004). In normal B cell differentiation, naïve B cells are activated by antigen through the B cell receptor, and by CD4+ T cell help through the CD40 receptor, so that they proliferate and progress through a germinal centre reaction in lymphoid follicles to become antigen-specific memory B cells. Remarkably, EBV expresses two proteins, latent membrane protein 2A (LMP2A) and LMP1, which mimic the antigen-activated B cell receptor and the activated CD40 receptor, respectively (Mancao and Hammerschmidt, 2007; Rastelli et al., 2008). These drive naïve B cells through a germinal centre reaction, independent of antigen and T cell help, to become latently infected memory B cells (Thorley-Lawson and Gross, 2004). Terminal differentiation of the latter into plasma cells initiates the lytic replicative cycle of EBV with the production of infectious virus (Laichalk and Thorley-Lawson, 2005). EBV is normally kept under tight control by EBV-specific immune responses, especially cytotoxic CD8+ T lymphocytes that eliminate proliferating and lytically infected B cells (Hislop et al., 2007). In the developing

http://brain.oxfordjournals.org/content/132/12/3196

 

[heapsreal]

Professor Michael Pender graduated from The University of Queensland in 1974 with First Class Honours in Medicine and a University Medal. Over the next six years he trained as a physician and neurologist at the Royal Prince Alfred Hospital and St Vincent's Hospital, Sydney, and became a Fellow of the Royal Australasian College of Physicians in 1981. During his clinical training he developed a keen interest in multiple sclerosis which has continued since then.
After completing clinical training in neurology, he commenced research on experimental autoimmune encephalomyelitis under the supervision of Professor Tom Sears at the Institute of Neurology, Queen Square, London. In 1983 he was awarded a PhD from the University of London and Queen Square Prize for Research. From 1984-1986 he continued this research as a Research Fellow at the John Curtin School of Medical Research, Australian National University, Canberra, in the Department of Experimental Pathology chaired by Professor Peter Doherty, Nobel laureate. In 1987 he was appointed Senior Lecturer in the Department of Medicine, The University of Queensland, at the Royal Brisbane Hospital. In 1989 he was awarded a Doctorate of Medicine from The University of Queensland for research on experimental autoimmune encephalomyelitis and was promoted to Reader in Medicine. In 1995 he was promoted to Professor of Medicine (Personal Chair), The University of Queensland. He also held the position of Director of Neurology, Royal Brisbane and Women's Hospital, from 1992-2005. He is Director of The University of Queensland Multiple Sclerosis Research Centre and an Honorary Senior Principal Research Fellow at the QIMR Berghofer Medical Research Institute, and directs the Multiple Sclerosis Clinic at the Royal Brisbane and Women's Hospital. In 2006 he was awarded the Multiple Sclerosis Australia Prize for Multiple Sclerosis Research - 'For outstanding commitment and dedication to research into the cause and cure of Multiple Sclerosis in Australia'. In 2011 he received the John H Tyrer Prize in Internal Medicine, The University of Queensland, for research in the field of Internal Medicine.

He's no dummy??
http://multiple-sclerosis-research.blogspot.com.au/2014/02/guest-post-professor-michael-pender.html

 

[DanME]

In my opinion the Ebstein-Barr-Virus is not always benign and never was. Probably the virus has infected humans for hundred of thousands (maybe even millions) of years and is extremely well adapted to men. A successful virus is not one, which kills fast (like e.g. Ebola), because it kills itself by killing its host, but one, which is able to stay silently in the host for a life time and infects nearly the entire population (like EBV). So the virus has learnt some tricks during our evolution to survive and avoid the total destruction by the immune system. During this process a lot of things can go wrong and disrupt the balance between the virus and the host.

There is a lot of evidence, that EBV is responsible for some cancer types (like Lymphoma, Hodgkin, Burkitt and cancer of the throat). EBV loves to hide in B Cells and in throat tissue. And sometimes EBVs hiding mechanisms probably disrupt the cells inner balance and if some other factors come together it leads to cancer. I would not be surprised, if EBV can lead B-Cells to autoimmunity.

I think there is still a lot to learn about the fine mechanisms EBV uses to be so successful in humans. And our diagnostics of reactivation are probably still limited.