Figure 2.

Bystander suppression.

As ASIT cannot achieve full antigen coverage, they rely on bystander suppression as a key mechanism, through which immuno-regulatory T cell populations (mostly CD4+ Tregs) induced under appropriate conditions (left) can migrate to disease-relevant sites (e.g., pancreatic lymph nodes and pancreas; right), find immunogenic APCs that present their epitopes, downregulate the stimulatory function of these APCs and suppress autoreactive T cells that are concomitantly engaged by these APCs and/or prevent later stimulation by these APCs. As the diversity of epitopes presented by these APCs increases, the diversity of autoreactive T cells suppressed also increases. If APCs at these sites all present a very diverse set of epitopes, fewer epitopes may be needed for ASIT. Infectious tolerance is achieved when suppressed T cells themselves are turned into regulatory T cells, which is a difficult yet ideal scenario to achieve.