And it is also in the thymus that occurs the selection of T lymphocytes that will or will not be released into the body. Because not all of them mean well - far from it. “The thymus eliminates self-reactive T cells, also called ‘forbidden’ clones. This concerns 95% of T cells generated at random in the thymus”, Vincent Geenen points out. “The thymus filters and lets through a mere 5% of cells, those that are self-tolerant. It is also capable of generating regulatory T (Treg) cells that inhibit forbidden T lymphocytes in the periphery that might have escaped the thymic filter". Thanks to this double control, the thymus prevents the adaptive immune system from turning against the body. “An increasing number of experimental arguments now reinforce this completely new concept according to which a defect in the intrathymic programming of central tolerance favours the development of autoimmunity, especially against pancreatic beta cells that secrete insulin”, the professor continues.

It’s a question of genes, but that’s not all!

Type 1 diabetes (T1D) develops in people who are genetically predisposed to this disease. “There are more than 20 genetic susceptibility loci”, Vincent Geenen explains. “But while we know that the genetic factor is important, it's not sufficient to cause the development of T1D", he continues. In identical twins, the concordance rate is only 45% for this disease. Therefore, there are other factors that favour the emergence of T1D. “In particular, environmental factors and among those different viruses including those from the family of enteroviruses, such as coxsackieviruses”, Vincent Geenen stresses. “We have known since the 1980s that there are diabetogenic viruses and epidemiological studies have shown proof of a correlation between recent infections by coxsackieviruses and the incidence of T1D”, the professor explains.

Besides these epidemiological studies, there is a north-south gradient in the incidence of T1D. “In Scandinavian countries, the incidence of T1D is approximately 50 cases for 100 000 inhabitants compared with 8 in Belgium. The lowest incidence is observed in African countries”, Vincent Geenen emphasises. The frequency of infection by enteroviruses is greater in the north than in the south of the planet which, according to some theories, could partially explain the existence of this gradient.

A disturbance in the tolerogenic function of the thymus?

While coxsackieviruses do indeed seem to play a role in the appearance of T1D, the mechanisms by which they act remain unknown. The hypothesis that Professor Geenen and Professor Didier Hober from the University of Lille have been investigating for more than 13 years, mainly as part of the Eurothymaide programme, is as follows: Coxsackieviruses infect the thymus and cause an imbalance in the tolerogenic function of the latter. “In 2002, Fabienne Brilot, a doctoral student at ULg who now teaches at the University of Sydney, demonstrated that coxsackievirus B4 (CVB4) is capable of infecting the thymus epithelial cells and of reproducing therein. Her work also helped to reveal a direct harmful effect of CVB4 on immature lymphocytes in the thymus (thymocytes) which differentiate into effector T lymphocytes”, Vincent Geenen stresses.