g., chronic rejection vis-a-vis chronic viral hepatitis).65 The concept that was developed from transplant Selleckchem ABT263 and infection models was generalized in the following way: “The migration and localization of antigen govern the immunologic responsiveness or unresponsiveness against infections, tumors, or self—and against xenografts or allografts.”65 In this view, all outcomes in the divergent circumstances of

transplantation, including those of microchimerism,150,171,172 were determined by the balance established between the amount of mobile donor leukocytes with access to host lymphoid organs and the number of donor-specific cytolytic T lymphocytes induced at the lymphoid sites (Fig. 11, inner graph).65 Long-term organ alloengraftment with this generalizable paradigm was a highly variable form of leukocyte chimerism-dependent tolerance, the completeness of which could be inferred from the amount of immunosuppression necessary to maintain stable function and structure of the transplant (Fig. 11). In a second article with Zinkernagel, the Pittsburgh-Zurich immunologic paradigm provided a road map for improved therapeutic strategies of transplant patient management based on two principles: recipient pretreatment and the least possible use of post-transplant immunosuppression.68 When applied clinically for different

kinds of organ transplantation,69 these strategies have minimized, or in some cases eliminated, the burden of chronic immunosuppression.173-178 More rational approaches also were developed for the treatment of opportunistic infections caused by noncytopathic KU-60019 molecular weight microorganisms.70,168,179 A second trend coincided with and was empowered by the rise

of the Internet. One of the mandates of the 1984 National Transplant Act was the formation of an Organ many Procurement and Transplantation Network (OPTN). Another was the development of a Scientific Registry of Transplant Recipients (SRTR) with which patient and graft survival could be quantified from center to center along with center-specific parameters. After the Department of Health and Human Services (DHHS) awarded the contract for both functions to the United Network of Organ Sharing (UNOS), disputes about organ allocation within the appointed UNOS committee prevented the development of the required plan. In order to avoid a UNOS default of contract, a document was pieced together from two articles that were “in press”, which described the renal180 and nonrenal181 distribution systems already in place in Pittsburgh. In the contract derived from these manuscripts and presented to DHHS on the eve of the deadline, the overwhelming factor for liver distribution was recipient urgency of need.181 In contrast, time waiting dominated kidney distribution with major credit for HLA matching only when this was complete.