Specially altered red blood cells could be used to help retrain the immune system in people with type 1 diabetes and even help combat the disease in the future.
Scientists in the United States have successfully genetically modified red blood cells in mice to carry specific antigens on the surface of beta cells that trigger inappropriate immune responses.
This has allowed them to alleviate two autoimmune diseases; type 1 diabetes and multiple sclerosis with techniques that are similar to desensitisation where an allergen is given repeatedly at low doses to teach the immune system that it is harmless.
The researchers from the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, used red blood cells as a mediator inducing tolerance of T cells towards the antigens they were likely to recognise as foreign.
The genetic modification specifically involved re-engineering the red blood cells with a protein sequence that code for a particular antigen and once transfused into the mice, the antigens masqueraded as the red blood cells’ own and thus were tolerated.
‘This a very promising step in the development of therapies for autoimmune diseases. If this type of response is also true in humans, then it could make a lot of these therapies possible for these diseases and similar conditions,’ said Harvey Lodish, a professor of biology and a professor of biological engineering at MIT.
Inappropriate immune responses cause scores of autoimmune diseases such as type 1 diabetes in which the body destroys its own cells. Although tolerance induction until now the technique has been fraught with problems, including how to deliver the antigenic peptides to their destination before they are degraded or beset by immune cells.
The scientists have found that red blood cells are particularly well suited for the delivery of molecules throughout the body. Not only do these cells quickly access almost every tissue, they are also recycled every month in mice and four months in humans without triggering an immune response against them.
For the new process they drew blood from a mouse, used sortagging to decorate the red blood cells with the antigens that trigger the harmful immune response, and transfused the altered red blood cells back into mouse models of type 1 diabetes and MS. The entire process was completed in about an hour.
In mice, the transfusions reduced symptoms of disease and even a single injection prior to the onset of disease could prevent further symptoms. However, although antigenic peptides can be effective in stimulating the induction of tolerance, the mechanism responsible is not well understood at the cellular and molecular levels.
‘Essentially what we’re doing is hijacking the red blood cell clearance pathway, such that the foreign antigen masquerades as the red blood cells’ own, such that these antigens are being tolerated in the process,’ said graduate student Novalia Pishesha.
According to Hidde Ploegh of Boston Children’s Hospital, the research could lead to future insights into how the immune system regulates itself and how that sometimes goes awry. ‘The Kell protein, which we use as an anchor point for many of our modifications, is a blood group antigen, and by its very nature shows that the immune system can distinguish red blood cells from genetically disparate individuals This technique may be an interesting way to explore how the immune system distinguishes self from non-self,’ added Ploegh.
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