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Given that viruses, especially EBV and HHV6a, are implicated in the pathogenesis of MS, this research on interleukin-21 seems relevant. IL-21 has been studied in the context of MS. I put one Pubmed abstract (there are more) below the article.


Chronic Infection Now Clearly Tied to Immune-System Protein

June 13, 2009 -- The reason deadly infections like human immunodeficiency virus (HIV) and hepatitis C never go away is because these viruses disarm the body’s defense system. Researchers at the University of Alabama at Birmingham (UAB) have discovered that a key immunity protein must be present for this defense system to have a chance against chronic infection.

Research up to now has tried but failed to decipher the cross-talk between ‘killer T-cells’ and ‘helper T-cells’ in the fight against viruses. The new UAB study finds this cross-talk can only happen in the presence of interleukin-21, a powerful immune system protein. If interleukin-21 is missing for whatever reason, then the immune system’s anti-viral efforts fail, said Allan Zajac, Ph.D., an associate professor in UAB's Department of Microbiology and lead author on the study.

The findings are published in the journal Science.

“Adding interleukin-21 back in stimulates the immune response and controls the infection,” Zajac said. “We demonstrate that the loss of this protein prevents the control of the infection and diminishes the function of the killer T-cells, specifically CD8 T-cells.”

The study mice were treated for lymphocytic choriomeningitis, a viral infection of the membranes surrounding the brain and spinal cord. Measurements were taken for two types of T-cells, CD4 and CD8 T-cells, before and after the mice were treated with interleuikin-21.

“Interleukin-21 served as the key messenger between the T-cells, whereas before we didn’t know exactly how the two types of cells communicated with each other,” Zajac said. The CD4 T-cells help the immune system do its job by boosting CD8 T-cells’ ability to fight and kill viruses.

Co-authors on the study include John Yi and Ming Du, Ph.D., both of UAB’s Department of Microbiology. Research funds came from the National Institutes of Health.

Source: University of Alabama at Birmingham

http://www.physorg.com/news164081303.html


IL-21 modulates CD4+ CD25+ regulatory T-cell homeostasis in experimental autoimmune encephalomyelitis.

Scand J Immunol. 2008 Jan;67(1):37-46.
Piao WH, Jee YH, Liu RL, Coons SW, Kala M, Collins M, Young DA, Campagnolo DI, Vollmer TL, Bai XF, La Cava A, Shi FD.
Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.

The homeostasis of CD4+ CD25+ regulatory T cells (Tregs) depends on the cytokine interleukin (IL)-2. As IL-21 shares sequence homology with IL-2 and the IL-21 receptors contain a gamma-chain common to IL-2, we hypothesized that IL-21 could also affect the homeostasis of Tregs. We tested this hypothesis in experimental autoimmune encephalomyelitis (EAE), an animal model of relapsing-remitting human multiple sclerosis.

We show that blockade of IL-21 in SJL/J mice before and after the induction of EAE enhances the influx of inflammatory cells into the central nervous system (CNS). The blockade of IL-21 leads to proliferation of proteolipid peptide (PLP(139-151))-autoreactive CD4+ T cells, which are capable to cause severe EAE in adoptively transferred recipient mice. Conversely, Tregs from mice where IL-21 was blocked, lose their capacity to prevent EAE induced PLP(139-151)-reactive T cells.

Notably, direct effects of IL-21 on Tregs are confirmed by studies of blockade of IL-21 in mice expressing a green fluorescent protein 'knocked' into a Foxp3 allele, in which a reduction of the number of Tregs and a downregulation of their frequency and expression of Foxp3 are observed. These data suggest a role of the IL-21/IL-21R axis in the homeostasis of Tregs in CNS autoimmunity.