We have previously discussed the importance of T cells in the initiation and maintenance of multiple sclerosis.  For example, it is known that CD4 T cells infiltrate the central nervous system of patients with multiple sclerosis and that through secretion of cytokines they induce microglial activation (associated with glutamate toxicity), as well as directly contribute to demyelination. 

An interesting component of the immune system that is only recently beginning to attract significant attention is the complement cascade.  This series of proteins is activated either by antibodies, or by proteins that secrete a “danger” signal to the body.  The activation of the complement cascade results in the formation of an “arrow-like” protein structure that inserts itself into the cellular membrane and results in the killing of the target cell.  This protein structure is called the “membrane attack complex”.

Usually immunologists think of complement as a means of the immune system clearing bacteria and other pathogens, however a recent study (Li et al. Augmenting DAF levels in vivo ameliorates experimental autoimmune encephalomyelitis. Mol Immunol 2009 Aug 4) demonstrated that complement may actually play a role in multiple sclerosis, or at least in the animal model of multiple sclerosis.

The investigators began by reporting data that in the experimental allergic encephalomyelities (EAE) model, when the mice are knocked out for the complement inhibitor decay accelerating factor (DAF), then the extent of autoimmune-mediated damage to the central nervous system is greatly amplified as compared to wild-type animals. 

If lack of the complement inhibitor exacerbates disease, it would seem logical that higher concentrations of the inhibitor may suppress disease.

The investigators generated DAF-transgenic mice, that is, mice that express high levels of the complement inhibitor DAF all throughout their bodies.  They observed that dendritic cells from DAF transgenic mice were poor stimulators of T cells.  This is an interesting observation because to my knowledge this is the first I see about complement affecting T cell proliferation.

The authors demonstrated that in contrast to wild-type (normal) mice, mice that were transgenic for DAF had reduction in inflammation and multiple sclerosis-like symptoms after induction of EAE with the administration of myelin oligodendrocyte glycoprotein antigen.

In conclusion this current study seems to suggest that augmenting levels of complement inhibitors may be a useful method of approaching multiple sclerosis.  Conversely, these data may stimulate research into small molecule inhibitors of complement activitors.  This reminds me…one of the well known complement inhibitors is cobra venom factor !  In fact, Tereny et al actually have a paper (Transient decomplementation of mice delays onset of experimental autoimmune encephalomyelitis and impairs MOG-specific T cell response and autoantibody production. Mol Immunol. 2009 Feb 6) demonstrating that cobra venom factor has some positive effects on the relapse remitting SJL model of multiple sclerosis.