Infection, Rejection, and the Connection

Abstract

Solid organ transplantation is a life-saving treatment for people with end-stage organ disease. Immune-mediated transplant rejection is a common complication that decreases allograft survival. Although immunosuppression is required to prevent rejection, it also increases the risk of infection. Some infections, such as cytomegalovirus and BK virus, can promote inflammatory gene expression that can further tip the balance toward rejection. BK virus and other infections can induce damage that resembles the clinical pathology of rejection, and this complicates accurate diagnosis. Moreover, T cells specific for viral infection can lead to rejection through heterologous immunity to donor antigen directly mediated by antiviral cells. Thus, viral infections and allograft rejection interact in multiple ways that are important to maintain immunologic homeostasis in solid organ transplant recipients. Better insight into this dynamic interplay will help promote long-term transplant survival.

Figure 1:. Development of heterologous immunity.

A) A naïve T cell pool encountering viral antigen will proliferate to form an effector response, and contract to the memory phase once the infection is under control. B) T cell receptor clones that cross-react with a different virus (orange TCR clone, purple virus) can mount a heterologous response to that virus. C) Upon exposure to alloantigen (red cell), T cell receptor clones (green) that cross-react to allo can mount a heterologous response to alloantigen. Note: allorecognition can be mediated through either direct or indirect antigen presentation, as described in the text. For simplicity, we only show direct presentation in this figure.