While accelerating the development of new tolerogenic therapies is the ultimate goal of the ITN, this will not be entirely possible without a greater understanding of the basic biological processes responsible for creating a tolerance state in human disease. While there is a wealth of data with regards to the mechanisms at work in tolerance induction in small animals, little exists within the realm of human clinical experience. Thus, each clinical trial sponsored by the ITN is matched with a corresponding set of mechanistic studies designed to elucidate the mechanisms of the induction, maintenance and/or loss of tolerance, and to identify surrogate markers of tolerance in humans.

Since its inception in 1999, the ITN has moved quickly to develop an infrastructure that would support mechanistic investigations in its clinical studies. This infrastructure is composed of a series of Core Facilities that serve all clinical investigations within the ITN, which have been developed with the following guiding principles:

Assay centralization when possible, for quality control purposes

Provide a centralized sample repository for storage and processing of patient materials

Ensure rapid data dissemination to contributing PI’s

Central data collection for higher order analyses

Mechanistic model building

With such standardized and centralized facilities, the ITN is well-positioned to allow cross-trial and cross assay comparisons as samples become available from clinical trials and as data begins to accumulate. In addition, the ITN is committed to the further development of additional facilities that would advance the understanding of the tolerance state in humans.