The innate immune system in allograft rejection and tolerance

Abstract

As T cells alone are both necessary and sufficient for the rejection of virtually all allogeneic tissues, much of transplantation immunology has focused on cells of the adaptive immune system. During the past decade, advances in our understanding of innate responses to pathogen-associated molecules have spurred a "rediscovery" of innate immunity. Fueled by this, an increasing body of literature has emerged in which the role of the innate immune system in allograft rejection and tolerance has been examined more closely. This review will give an overview of recent studies and emerging concepts of how the cellular components of the innate immune system participate in the immune response to solid organ transplantation. These important studies highlight the complex interplay between diverse cells of the immune response and provide the basis for optimal strategies of tolerance induction.

FIGURE 1

Innate immune responses in allotransplantation. Soon after solid organ transplantation, Ag-independent insults to the allograft caused by organ procurement and ischemia/reperfusion injury promote immunogenicity via danger signals that lead to the activation of donor-derived APCs. The direct pathway of allorecognition is depicted in which “passenger” DCs undergo functional maturation in response to danger-associated molecules and then traffic to the T cell areas in recipient lymphoid tissue. Thus, naive alloreactive T cells become stimulated, transition to effectors, and engage the graft directly. Other cells of the innate immune system, such as neutrophils, macrophages, and NK cells, rapidly infiltrate the allograft in response to inflammatory signals and promote further injury either by their own proinflammatory mechanisms or by supporting the activity of alloreactive T cells.