Old game, new players: Linking classical theories to new trends in transplant immunology

Abstract

The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the setting of disorders such as autoimmunity and transplant rejection. In light of the latter, although research has long uncovered main concepts of allogeneic recognition, immune rejection is still the main obstacle to long-term graft survival. Therefore, in order to define effective therapies that prolong graft viability, it is essential that we understand the underlying mediators and mechanisms that participate in transplant rejection. This multifaceted process is characterized by diverse cellular and humoral participants with innate and adaptive functions that can determine the type of rejection or promote graft acceptance. Although a number of mediators of graft recognition have been described in traditional immunology, recent studies indicate that defining rigid roles for certain immune cells and factors may be more complicated than originally conceived. Current research has also targeted specific cells and drugs that regulate immune activation and induce tolerance. This review will give a broad view of the most recent understanding of the allogeneic inflammatory/tolerogenic response and current insights into cellular and drug therapies that modulate immune activation that may prove to be useful in the induction of tolerance in the clinical setting.

Keywords: Transplant immunology; Immune rejection; Inflammation; Adaptive immunity; Innate immunity; Graft tolerance

Core tip: Although the basic mechanisms of transplant allorecognition have been the object of intense study for the last 80 years, graft rejection is still an important obstacle in clinical practice. This review focuses on the principal concepts of transplant immunology and how they apply to the most recent discoveries in the field. It also reviews current treatments used to prolong graft survival and recent approach trends toward tolerance induction in the translational setting.