Fig. 2.

Recipient immune response to transplanted islets. The recipient immune system is activated through the initial surgical trauma and introduction of foreign material. In addition, damage to the islets causes the release of antigen (Ag) into the environment. The innate immune system responds through macrophage and neutrophil activation, causing inflammation in the microenvironment and infiltration of additional immune cells into the graft. Macrophages and neutrophils initiate a cascade through the release inflammatory cytokines and reactive oxygen species that activate the antigen-presenting cells (APCs) and damage the islet. Active APCs activate helper T cells (CD4) that continue to activate cytotoxic T cells (CD8), which destroy the islet. Regulatory T cells maintain APCs and helper T cells in inactive states, preventing the adaptive immune response from destroying the islet. The diagram to the right depicts the timeline and types of infiltrating cells in the graft site following transplantation. A number of interventions aimed at interrupting the immune cascade are listed to the right, and their point of action is indicated by the corresponding numbers on the diagram. These interventions are detailed in the article text