A mysterious X cell, part of the immune system that sometimes goes rogue and attacks the pancreas, has been proposed to explain type 1 diabetes. However, like the possible planet with the same designation, years of failure to find the object in question have inspired widespread doubts it exists. So a claim to have discovered the X cell in its natural habitat vindicates those who have kept faith and may open a path towards treatment.
Like other autoimmune conditions, type I diabetes involves the immune system treating healthy cells like dangerous invaders. In this case, the innocent victims are the insulin-producing beta cells of the pancreas, but that doesn’t explain what causes such a harmful and specific error.
Dr Abdel-Rahim Hamad of Johns Hopkins University suspects a new type of cell he has discovered is responsible. “The cell we have identified is a hybrid between the two primary workhorses of the adaptive immune system, B lymphocytes and T lymphocytes,” Hamad said in a statement. These hybrids, dubbed dual expressor (DE) lymphocytes, have receptors characteristic of both B and T cells on their surfaces.
Although he is not yet ready to claim definitively his discovery is the cause of type I diabetes, Hamad believes he has “strong evidence” this is the case.
When bound on the surface of white blood cells, insulin can trigger a response in T cells. It’s been proposed this leads them to see the hormone, and the cells that make it, as a threat. “However, our experiments indicate that it is a weak binding and not likely to trigger the strong immune reaction that leads to type 1 diabetes,” Hamad said.
IBM’s Dr Ruhong Zhou co-wrote the paper in Cell with Hamad announcing the hybrid’s discovery. Zhou created a computer model of an insulin mimic whose tighter bonds are designed to trigger a stronger reaction. Simulations suggested this would indeed have an effect 1,000 times stronger than ordinary insulin.
However, B cell receptors on DE lymphocytes produce a peptide, x-ld, which Zhou found binds 10 times more powerfully to the T cell receptors than the molecule he designed for the purpose. So the peptide produced by one set of receptors appears to be the what causes other receptors, on the same cell, to turn against the body’s own organs.
This makes DE lymphocytes a candidate for causing type 1 diabetes, and Hamad’s confidence in his theory rose when he found higher concentrations of them and x-ld in the blood of people with type 1 diabetes.
If Hamad’s further research confirms DE lymphocytes’ role, the race will be on to find immunotherapies that eliminate or tame them so diabetics can produce their own insulin in peace.