Escaping from rejection

Abstract

Since the earliest days of transplantation, immunobiologists have sought means to prevent recognition and rejection of foreign tissue. The goal of these strategies is the retention of recipient immune function while selectively avoiding graft injury. Although considerable theoretical and technical problems remain, an analogous problem and solution already exists in nature. Here, we discuss the mechanisms by which organisms preclude or control autotoxicity, and for each, consider the corollaries between prevention of autotoxicity and graft rejection. Further study of these controls, including structural and conditional tolerance and accommodation, will offer insight into new therapies for allo- and xenotransplantation.

Figure 1

A. Structural tolerance. The potential repertoire of the immune system (T and B cell receptors) is more diverse than the manifest repertoire, as autoreactive clones are deleted during development. B. Conditional tolerance. The environment in which an antigen is recognized determines whether the naïve cell becomes anergic, or goes on to either an effector or tolerogenic phenotype. APC, antigen presenting cell. C. Accommodation. Low-level injury (by complement, perforins, toxins, or other stimuli) causes cellular adaptations leading to survival in the face or higher-level insults.