B and T cells are the two known lymphocytes of the immune system. But a team led by Johns Hopkins University researchers has identified a new cell type that looks like a hybrid of the two main immune cells. And the rare immune “X cell” may play a key role in the development of Type 1 diabetes, they found.
Scientists have long known that Type 1 diabetes happens when the immune system mistakenly attacks insulin-producing beta cells in the pancreas. However, the underlying mechanism at the cellular level was not clear.
The team believes the findings of what they call a dual expresser (DE) cell—and a protein that it produces—shed some light on the mechanism and lay the groundwork for developing immunotherapies against Type 1 diabetes. They published the findings in the journal Cell.
“What is unique about the entity we found is that it can act as both a B cell and a T cell,” the study’s senior author and Johns Hopkins pathologist Abdel-Rahim Hamad said in a statement. “This probably accentuates the autoimmune response because one lymphocyte is simultaneously performing the functions that normally require the concerted actions of two.”
Normally, bacteria, viruses and other foreign invaders are first processed by a white blood cell called the antigen presenting cell (APC). Antigenic proteins are exposed on the surface of APCs and then identified—and latched onto—by T-cell receptors and B-cell receptors that activate T cells and B cells, respectively.
In comparison, the DE cells express both receptors, the team found. To confirm their characteristics, the researchers made clones of DE cells and found that every clone possessed both receptors.
“It is well accepted that insulin is seen as an antigen by the T cells and that this occurs when the hormone is bound to a site on the APC known as HLA-DQ8,” Hamad explained. “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 and colleagues noticed a protein encoded by the B-cell receptor present on the DE cell surface. Called the x-ld peptide, the protein could replace insulin and bind so tightly to DQ8 that it can elicit a CD4 T-cell response 10,000 times stronger, the team found, using computer simulations by Ruhong Zhou and his team at the IBM Thomas J. Watson Research Center.
Many different therapeutic methods are being examined to treat Type 1 diabetes. Within the regenerative medicine group, researchers at the University of Geneva recently converted other pancreatic cells into insulin-producing beta cells. Provention Bio is developing a vaccine based on the idea of a possible link between enterovirus infections and the autoimmune disorder. And Pfizer just licensed AnTolRx's nanoparticle therapeutics designed to induce immune tolerance to avoid attacks on beta cells.
Hamad’s team believes its findings could offer a biomarker that helps screen individuals at risk for developing Type 1 diabetes. “It also is possible that this study could lay the groundwork for developing immunotherapies that target DE cells for elimination or genetically alter the lymphocytes so that they cannot stimulate an immune response,” study co-author Thomas Donner said in a statement.