Rejection of a transplanted organ, triggered by infection, may not mean that a subsequent transplant will also be rejected, reports a study in mice published in Nature Communications. Rejection occurs when the immune system sees a transplanted organ as foreign and attacks it. In some recipients this happens within weeks and further transplants result in an even faster rejection due to the alert state of the immune system. In other cases, immune tolerance is initially established but the graft gets rejected after months or years, which may be triggered by infections. The assumption was that in these cases, a second transplant would also be quickly rejected and that loss of tolerance is permanent.
Anita Chong, Maria-Luisa Alegre and colleagues gave mice a heart transplant and allowed immune tolerance to establish, then challenged the mice with a bacterial infection. The infection triggered transplant rejection in half of the animals. However, the authors discovered that the immune activation was only transient: once the immune system eliminated the bacteria, it spontaneously returned to the earlier state of immune tolerance and accepted another heart transplant. These results describe a condition where tolerance dominates over the memory of transplant rejection and, if they are borne out in human patients, may have implications for therapeutic approaches to transplantation, autoimmunity and cancer.