The bidirectional paradigm of transplant immunology.

Abstract

Until 1992, the conventional view of transplantation immunology was what we have referred to as the one-way paradigm (Fig. 1A and B), a conceptual framework that had been extrapolated from the neonatal tolerance model of Billingham, Brent, and Medawar.1,2 In Medawar’s defenseless recipient experiments, and in the parent to offspring F1, hybrid and recipient cytoablation models (Fig. 1A), it was learned in the 1950s that the risk of lethal graft-versus-host disease (GVHD) after splenocyte or bone marrow transplantation was directly proportional to the degree of MHC incompatibility. FIGURE 1 Transplantation immunology as seen with the conventional one-way paradigm (A for bone marrow and B for whole organ transplantation). The two-way paradigm is shown in C (whole organ) and D (bone marrow transplantation). As early as 1959, it was known that all the same rules applied when whole organs containing immunologically active cells, such as the intestine, were transplanted. Thus, any kind of hematolymphopoietic transplantation was conceived to be an essentially one-way cellular transaction, yielding either GVHD, rejection, or tolerance.