Autoimmunity, such as multiple sclerosis, is characterized by the immune system attacking components of the body.  Normally the body has numerous mechanisms of protecting itself from this, which we have previously discussed.  One way that the immune system “self regulates” itself is by a special type of T cell, called that T regulatory (Treg) cell.  The T cell receptor (TCR) of Treg cells is usually activated by recognition of proteins of the body.  This is an interesting point.  “Normal” T cells are usually turned on when their T cell receptor recognizes parts of proteins (called peptides) that are found on components that do not belong in the body.  Unfortunately in situations such as multiple sclerosis, rheumatoid arthritis, or Type 1 Diabetes, the T cells that are suppose to be activated by foreign peptides are activated by peptides that belong to the body (in multiple sclerosis the T cells are attacking components of the myelin basic protein which acts as an insulator around axons of the nerves).  The Treg cells, which recognize myelin basic protein are activated by the myelin basic protein components as well as by the presence of the conventional T cells being activitated.  What occurs is that the Treg cells attempt to suppress the destruction of the myelin by the normal T cells, through producing various chemical mediators, called cytokines, that suppress the effects of the conventional T cells.

So to try to state it in another way:  Conventional T cells activate the immune response and cause damage.  In the healthy situation, the conventional T cells cause damage to bacteria, virus infected cells, and cancer cells.  In the healthy situation Treg cells act as a protective mechanism so that in the cases that the conventional T cells start attacking components of the body, the Treg cells then inhibit the conventional T cells from doing this.  So another way of thinking about it is that the Treg cells are a “safety backup” so that the body does not attack itself.

So the question then becomes, what is going on in autoimmunity in general and specifically in conditions such as multiple sclerosis?  Are these Treg cells not doing their job properly?

There is a recent paper that was published (Korporal et al. Interferon beta-induced restoration of regulatory T-cell function in multiple sclerosis is prompted by an increase in newly generated naive regulatory T cells. Arch Neurol. 2008 Nov;65(11):1434-9) assessing Treg activity in 18 healthy volunteers and 20 patients with relapse-remitting multiple sclerosis. 

When comparing Treg activity between the healthy volunteers and the relapse remitting multiple sclerosis patients they found that ability of Treg to suppress immune response was deficient in the multiple sclerosis patients as compared to controls.

But the investigators then took the study a step further.  They assessed the Treg activity in patients before and after starting to take interferon beta therapy (Avonex is a type of interferon beta).  They found that both at 3 and 6 months after administration of interferon beta the suppressive activity of the Treg was restored to normal levels.  See figure below. 

Restoration of Treg Activity after Interferon beta Therapy

Given that mesenchymal stem cells have been demonstrated to induce Treg activity, and that adipose stem cells actually have high concentrations of Treg, two interesting questions arise.  Firstly, can interferon beta therapy synergize with stem cells?  Secondly, can autologous adipose stem cell therapy serve as a substitute for interferon beta therapy? 

Other thoughts come to mind as well, such as, can if indeed Vitamin D is associated with Treg activity, would it synergize or antagonize the effects of interferon beta on the Treg and actually on the clinical situation?

Tags: autoimmunity, CD4+ CD25+, Fox P3, multiple sclerosis, T regulatory cell, Treg

This entry was posted on Sunday, June 28th, 2009 at 3:32 am and is filed under Clinical Observation, Clinical Trials. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.