Increases in T-Cell Antigen Responsiveness Precede Clinical Diabetes
WESTPORT, CT (Reuters Health) May 11 – Just as the number of autoantibodies increases before the appearance of clinical diabetes, so does the extent of T-cell responsiveness to islet cell proteins, according to a report in the April 15th issue of the Journal of Immunology.
Acquired recognition of self-determinants, a process called intermolecular antigen spreading, accompanies the development of a number of autoimmune diseases, the authors note. The phenomenon as it applies to T cells before the development of diabetes has not been explored previously.
Seven of the 25 subjects developed clinical diabetes, the authors report, and all but two of them showed increases in autoantibodies and became positive for all four autoantibodies measured. One subject was already positive for all four.
T-cell responsiveness to islet proteins also increased among six of the subjects who developed clinical type 1 diabetes, the results indicate. The seventh subject who developed diabetes was already reactive against all 18 proteins measured.
Nine of the 18 subjects who have not yet developed diabetes showed an increase in the number of autoantibodies, the researchers note.
“Our data strongly support the conclusion that intermolecular spreading of T-cell and antibody responses to islet proteins occurs during the preclinical period of type 1 diabetes,” the authors conclude.
“What we think happens,” Dr. Brooks-Worrell told Reuters Health, “is that some initially reactive T cells participate in the damage to the islet cells, releasing more antigens. More reactive T cells are recruited and more damage ensues, leading to clinical diabetes.”
“The recently completed Diabetes Prevention Trial should help us to determine whether we can prevent the antigen spreading and thereby prevent or delay the development of diabetes,” Dr. Brooks-Worrell said. Results from that study, she said, are due in June.
“Ultimately, we hope to be able to tease out how the body controls what we see as a struggle between regulatory and destructive processes that occurs in diabetes and other autoimmune diseases,” Dr. Brooks-Worrell concluded.