Tolerogenic DC first, then autologeous cells for Diabetes Typ I

Diabetes Typ 1 is a disease where the insulin producing cells are deleted by the immune system itself. When one tries a therapy with genetically modified  or outlogues insulin-producing cells these will still be eliminated by the immune system that destroyed the insulin forming cells initially. There is a drastic way to suppress the entire immune system with immune suppressive drugs, but:

While the approach works for kidneys or for livers, those cells which make insulin are obviously sensitive to the drugs used and stop insulin production.  This leaves as the sole possibility to render the immune system itself to a state where it no longer rejects insulin forming cells, i.e. make the immune system tolerant.

A paper in Diabetes (doi: 10.2337/db13-0886) mentioned just this appraoch and some first steps in a mouse model: Fathman and colleagues describe the use of dendritic cells for this purpose.

The immune system acquire tolerance to self antigens via stochastic expression of all self proteins in medullary thymic epithelial cells (mTEC). These cells are characterized by the autoimmune regulator protein AIRE. T lymphocytes are told not to react to the antigens presented by AIRE positive cells. In the case of autoimmunity this situation is overcome and the autoreactive T and B lymphocytes develop. Injecting dendritic cells (DC) should remedy the situation. These DC could be stuffed with insulin. The scientist aim at the regulatory T lymphocytes which can be manipulated by DC from an immunogenic state back to tolerance.

This is an ambitious task. Since the knowledge about regulatory T cells has developed very far, it seems that the time is ripe to try tolerogenic therapies in patients. A successfully application for any antigen to become tolerogenic would open the paths to many monogenic diseases which are hampered by the lack of tolerance to allo- or xenoantigens (different within a species or across the species border).  One should wish that the time of tolerogenic therapies will soon come. This would be the first step for all the therapies which until now make heavy use of immune suppressive drugs. Allorejection of whole organs can not be treated that way, but those therapies where a single antigen is in question might.

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