Tyler AF, Mendoza JP, Firan M, Karandikar NJ. CD8+ T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease. PLoS One. 2013;8(6):e66772. Print 2013.
The exact mechanism of glatiramer acetate (GA, Copaxone®), an FDA-approved immunomodulatory therapy for multiple sclerosis (MS), remains unclear after decades of research. Previously, we have shown that GA therapy of MS induces CD8+ T cell responses that can potentially suppress pathogenic CD4+ T cell responses. Using a murine (IT IS MOUSE!!!!!!!) model of MS, experimental autoimmune encephalomyelitis (EAE), we now demonstrate that CD8+T cells are necessary in mediating the therapeutic effects of GA. Further, adoptive transfer of GA-induced CD8+ T cells resulted in amelioration of EAE, establishing a role as a viable immunotherapy in demyelinating disease. Generation of these cells required indoleamine-2,3-dioxygenase (IDO), while suppressive function depended on non-classical MHC class I, IFN-γ, and perforin expression. GA-induced regulatory myeloid cells, previously shown to activate CD4+ regulatory T cells in an antigen-independent manner, required CD8+ T cells for disease suppression in vivo. These studies demonstrate an essential role for CD8+ T cells in GA therapy and identify their potential as an adoptive immunotherapeutic agent.
I am so ancient that I remember when I first started immunology and CD8 cells were not called CD8 cells but suppressor/cytotoxic cells meaning they were killing machines and also were suppressors of the immune response. This was controlled by a bit of the major histocompatibility complex that was controlled by a region called the I-J region. Problem was that molecular biology came along and sequenced the region and there was no I-J where it was supposed to be and that was that for suppressor cells that could not be cloned at that time.
So then the dogma machine arrived and it became heracy to say suppressor cell. This became the domain of Th2 and then onto Treg cells, which is still flavour of the month.
I wonder if the tide is changing because in the past few weeks there have been lots of posts on CD8 suppressor cells so we are re-inventing the wheel. Has the generation of immunologists retired/died who remember CD8 suppressor and contrasuppressor (a suppressor cell that suppress a suppressor cell)
So onto another machine and this is our friend glaterimer acetate. This drug has had more mechanisms of action than I have had hot dinners. This mechanism of action has followed the trend of the month so now it is stimulating suppressor cells they inhibit the action of CD4 cells. Will we see a sea of complementary data on this?
But for all this immunological who-ha...surely it just needs to work a lot better than it does, because it always argues that the immunological mechanistic flavour of the month is not as important as the immunologists make out.
It you actually look at the so called therapeutic effect in this study (Figure 2) then surely it should have been a case of "Schtop" as it is a bit of an "Shania"
If the referees start making people tell us how many animals get sick and what are the scores rather than just feeding us these line graphs that can mean a lot or a little. it will save alot of our furry friends.
There is class I evidence for some active role in MS, but depletion of CD8 T cells alone has not been done yet.
Look forward to the next Mechanism of Action to be found.