In an article published in the Journal of Virology (1), Vincent Geenen, Didier Hober and their colleagues have recently found another answer. They have revealed that the infection of the thymus epithelial cells by CVB4 leads to a clear decrease in the transcription of the IGF2 gene (Insulin-like Growth Factor 2), a gene from the insulin family that intervenes in the programming of immune tolerance towards this entire family, especially during the foetal period. Thymic infection by CVB4 would therefore be responsible for a rupture in central immune tolerance to insulin and the beta cells that secrete this hormone.

Towards an anti-T1D vaccine

In order to check the specificity of the action of CVB4 on the expression of IGF2 in the thymic epithelial cells, scientists have increased the number of control experiments. “We looked at whether the same action of CVB4 was observed in other target cells of this virus. We analysed the effect of CVB4 on the expression of IGF2 by neuroblasts but no decrease in the expression of this gene was observed”, Professor Geenen explains. “In addition, we tested to see if other viruses caused a decrease in the expression of IGF2 in thymic epithelial cells, and this wasn’t the case", he continues.

Moreover, these results have the advantage of unifying three of Vincent Geenen’s laboratory major working hypotheses:
- Role of a dysfunction of the thymus that lies at the origin of the diabetogenic autoimmune response.
- Role of thymic IGF2 as a major tolerogenic factor of the insulin family, and
- The involvement of infection by CVB4 in the appearance of T1D.

With regards to the future stages of this research, scientists will now endeavour to reveal the mechanisms by which CVB4 induces a repression of the expression of IGF2 in the thymic epithelial cells. “It is necessary to identify the missing links between the receptor for the CVB4 virus on the surface of these cells and the decrease in the expression of IGF2”, Vincent Geenen specifies. But the professor’s team is now focusing first and foremost on the development of a new type of vaccine, a ‘negative or tolerogenic self-vaccine’ based on IGF2 that would reprogram immune tolerance to the endocrine pancreas beta cells and thus contribute to both the prevention and cure of T1D.

(1) Jaïdane H, Caloone D, Lobert PE, Sane F, Dardenne O, Naquet P, Gharbi J, Aouni M, Geenen V, Hober D. Persistent infection of thymic epithelial cells with coxsackievirus B4 results in decreased expression of type 2 insulin-like growth factor. J Virol. 2012 Oct;86(20):11151-62. Epub 2012 Aug 1.

(3) Geenen V, Mottet M, Dardenne O, Kermani H, Martens H, François JM, Galleni M, Hober D, Rahmouni S, Moutschen M. Thymic self-antigens for the design of a negative/tolerogenic self-vaccination against type 1 diabetes. Curr Opin Pharmacol. 2010;10:461-472.