Tissue Injury-Induced Initiation of the Adaptive Immune Response

Abstract

We read, with great pleasure, the article by Wood and Goto (1) and agree with the scientific content of their article, especially with their statement “Activation of elements of the innate immune system, triggered as a consequence of tissue injury sustained during cell isolation or organ retrieval and ischemia-reperfusion, will initiate and amplify the adaptive response.” We particularly enjoyed their article because it is in full agreement with our Injury Hypothesis posed in 1994/1996 (2, 3). The original Injury Hypothesis, as published in Transplantation in 1994 (2), held that the postischemic reperfusion injury to an allograft (in addition to its degree of foreignness) initiates and induces the adaptive alloimmune response, predominantly through injury-induced activation of antigen-presenting cells. The theory was extended and modified several times during subsequent years (4–7). Along with these modifications, we coined the terms Innate Alloimmunity in 2002 (4) and DAMPs in the sense of damage-associated molecular patterns in 2003 (5). In particular, we proposed that oxidative stress to the brain-dead donor organism and generation of reactive oxygen species during reperfusion of the allograft represent acute injurious events to the donor organ that, in turn, lead to acute rejection. By activation of donor/recipient Toll-like receptor-bearing dendritic cells of the innate immune system through interaction of damage-associated molecular patterns with Toll-like receptors, these events lead to initiation of adaptive alloimmunity (6). In a recently published review article, evidence is provided in support of the notion that prevention of oxidative allograft injury may operate as an efficient tool in the clinical situation to present alloantigens under subimmunogenic conditions within an intragraft noninflammatory milieu, thereby potentially generating tolerogenic dendritic cells able to induce regulatory T-cell-mediated innate allotolerance (7). Finally, the whole concept of the Injury Hypothesis, in light of the international literature on innate immunity currently available, has been thoroughly and comprehensively discussed in a monograph that was recently published (8). We thought it would be worthwhile to provide the reader of Transplantation with this information about the scientific history of the Injury Hypothesis: a note that may serve as a useful addendum to the excellent article by Wood and Goto. Walter G. Land 1 Konrad MeAmer2 1German Academy of Munich, Germany 2Former Institute for Surgical Research University of Munich Munich, Germany