Sunday, 23 December 2012

Research: Immune Tolerance in humans

Epub: Loo et al. High dose antigen treatment with a peptide epitope of myelin basic protein modulates T cells inmultiple sclerosis patients. Cell Immunol. 2012 Nov 27;280(1):10-15. doi: 10.1016/j.cellimm.2012.11.004.

One of the auto-antigens aberrantly targeted in Multiple sclerosis is myelin basic protein (MBP). In this study, chronic progressive multiple sclerosis (CPMS) patients receiving the experimental drug MBP8298, on a compassionate care trial, were examined before and after high dose peptide treatment for their circulating regulatory T-cell numbers and their responses to the common mitogens, phytohemagglutinin and poke-weed mitogen. Peripheral blood mononuclear cells (PBMCs) isolated from these patients before treatment displayed anergy upon stimulation with phytohemagglutinin; measured through reduced proliferation, IFN-γ and IL-17A secretion in an in vitro cell culture system. 6 Weeks and 6months after treatment their PBMCs displayed a reversal of anergy with phytohemagglutinin stimulation. There was also a marked increase in their CD4(+)CD25(+hi)FoxP3(+) T-cells regulatory T-cells. These results suggest that high dose MBP8298 treatment has a profound effect on the circulating T-cells of CPMS patients, capable of reversing peripheral anergy and establishing T regulation.

Phytohaemagglutinin is a T cell mitogen, which means it stimulates all T cells irrespective of their specificity i.e. irrespective of what things they recognise. Anergy means that the cells are unresponsive (which can be reversed by giving T cell growth factors such as interleukin 2). When this MBP peptide was given intravenously the cells became responsive, which in my opinion may not be a good thing if it makes self-aggressive cells respond to self. It also resulted in an increase of T regulatory cells. The question that begged to be answered was what happened to the MBP responsive cells. However this was irrelevant as this treatment did not effect progressive MS in the trials. This is not surprising as progressive MS does not seem to respond well to immunosuppressives, and also I am not convinced that MBP is the answer. However, it shows the approach is safe. So when applied to RRMSers it will be more interesting if one selects the right antigens.

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