Immunology

Hope for Type I diabetes patients

Print edition : June 21, 2019

Colourised scanning electron micrographs of a B and T lymphocyte shown with a fluorescent microscopy image of the “X lymphocyte”, a hybrid of the other two. Photo: NIAID/JHUSM

Besides the known B and T lymphocytes (types of white blood cells), which are the workhorse cells of the adaptive immune system, scientists have now established the existence of the long-suspected “X lymphocyte”, which had earlier been called Dual Expressor or DE cell. It is a hybrid of the B and T cells and may play a key role in the development of Type 1 diabetes.

A team comprising researchers from Johns Hopkins University School of Medicine (JHUSM), IBM Research and four collaborating institutions has made this discovery, which has been reported in the recent issue of the journal “Cell”. “Our findings not only show that the X cell exists, but that there is strong evidence for it being a major driver of the autoimmune response believed to cause Type 1 diabetes,” says Abdel-Rahim A. Hamad of JHUSM, one of the authors of the paper.

Type 1 diabetes, also known as juvenile diabetes or insulin-dependent diabetes, is a chronic condition in which the beta cells in the pancreas that produce insulin, the hormone that regulates a person’s blood sugar level, are destroyed. It is diagnosed mostly in childhood but is present at all ages. Hamad and his colleagues believe that X cells are responsible for it. However, they caution that more analysis is required to directly link the X cell to Type 1 diabetes.“What is unique about the entity we found is that it can act as both a B cell and a T cell,” says Hamad. “This probably accentuates the autoimmune response because one lymphocyte is simultaneously performing the functions that normally require the concerted actions of two.”

The research team came across these hybrid cells while they were looking for a specific type of B cell they had studied earlier in the blood of Type 1 diabetes patients. Using flow cytometry, they observed cells that present both B-cell and T-cell receptors on their cell surface, and upon further investigation they revealed that the cells also express genes specific to both B and T cell lineages.

Immunologists have opined that the presence of a cell that expresses both B-cell receptors and T-cell receptors and of its own is in itself very novel. These “dual expresser” (DE) cells were found more abundantly in Type 1 diabetes patients than in controls, explains Hamad. .“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,” says Thomas Donner, director of the Johns Hopkins Diabetes Centre and a co-author of the study. “We were willing to take the risk and look at something different, and now we may have taken the first steps toward finding new strategies to cure Type 1 diabetes,” he says. “We also may one day find that DE cells are involved in the pathology of other autoimmune disorders such as multiple sclerosis and rheumatoid arthritis.”

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