T regulatory cells that inhibit multiple sclerosis that are not T reg

Cambridge, MA -

Multiple sclerosis is mediated by autoimmune T cell responses against components of the myelin basic sheath, for example myelin basic protein, myelin oligodendrocyte protein, and phospholipid protein.  Stem cell therapy, especially with universal donor mesenchymal stem cells or endometrial regenerative cells, has potent for treatment of this disease, however these therapies are still not implimented on a widespread basis.  One treatment of multiple sclerosis that has been successful clinically is glatiramer acetate, which is a polymer of repeating peptides.  Its mechanism of action was not really figured out although numerou theories exist.  Nevertheless it has helped hundreds of thousands of patients.

In a recent paper (Stern et al. Amino acid copolymer-specific IL-10-secreting regulatory T cells that ameliorate autoimmune diseases in mice. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5172-6) immunological mechanisms of glatiramer acetate were examined in detail.

Mice were immunized with autoantigens and treated with glatiramer acetate and a specific type of it made by Peptimmune called FYAK.  T cell lines were made by in vitro restimulation.  It was found that the T cell lines were capable of protecting mice when administered into mice with ongoing disease, thus stimulating the authors to call the cells "T regulatory".

T cell lines responding to the glatiramer acetate were not "true" T regulatory cells since they lacked expression of FoxP3.  Interestingly the cells expressed CD30 and GITR, as well as the classical CD4+ CD25+ T regulatory cell markers.

The T cell lines produced the cytokines IL-10 and IL-13 but little IL-4.

Most strikingly, the T cells were antigen-nonspecific in their activity, at least in their in vivo activity.  The cells blocked autoimmune responses induced by a variety of different autoantigens.    These data provide some additional insight as to mechanisms of glatiramer acetate.  Given that mesenchymal stem cells stimulate T regulatory cells, it will be interesting to see if synergy of effect can be attained by adding these two approaches.