Infectious Antigen Specific Tolerance by Dendritic Cells

Wuhan, China -

The possibility of T regulatory cells inducing tolerance, both antigen specifically, and antigen-nonspecifically through the modulation of antigen presenting cell function has been previously established. What is more interesting is the concept of an antigen presenting cell being able to transfer tolerance without the intermediary of a T regulatory cell. In a recent paper (Xiang M et al. Insulin Administration Confers Diabetes-Preventive Properties to NOD Mice Derived Dendritic Cells. Immunopharmacol Immunotoxicol. 2007;29(3):451-64) this is exactly what was done.

The non-obese diabetic (NOD) mouse is a model for type 1 diabetes. The authors used the established procedure of pre-injection with subcutanous insulin in order to induce tolerance to insulin and thus protection from disease. It was observed that in protected mice the dendritic cells isolated were capable of preventing transfer of diabetes to naive NOD-SCID recipients.

Dendritic cells from mice that were made tolerant to insulin appeared to have upregulated expression of MHC II and B7.2, as well as increased ability to stimulate allogeneic T cells. Despite having an "activated" phenotype, the dendritic cells isolated from tolerant mice could elicit T regulatory cells, and has previously mentioned, could inhibit transfer of diabetes.

These data suggest that various tolerance induction procedures are capable of causing upregulation of activated phenotypes on antigen presenting cells. This is in contradiction with other studies in which tolerogenesis is associated with immature dendritic cells.