The Innate Immune System: Its Rediscovery before Toll Was Described

In 1994, in a prospective control trial in cyclosporinetreated, kidney transplant patients, we observed that treatment of a non-specific allograft injury (postischemic reperfusion injury) leads to a significant reduction in the incidence of both specific alloimmune-mediated allograft rejection and chronic allograft failure. From these convincing clinical data, we concluded in terms of an ‘argumentum e contrario’: it is the tissue injury that induces immunity. As from where we stand today in innate immunity research, these early clinical observations can be regarded as the discovery of the existence of a human innate immune system activated by tissue injury and preceding adaptive immunity. Copyright © 2013 S. Karger AG, Basel Current notions in immunology hold that not only pathogen-induced injury but any tissue injury activates the innate immune system leading to infectious/sterile tissue inflammation and preceding adaptive immunity [1–3] . With respect to these modern notions on a fundamental role of the innate immune system in inflammation and adaptive immunity, a peer-reviewed article that dealt with this issue already at an early stage published in Transplantation in 1994 appears to be of interest [4] . In this article, we described the existence of a defense system in humans (without calling it ‘innate immunity’) before first studies on the discovery of the innate immune receptor Toll were published [5, 6] . Interestingly enough, our article appeared just a few months before Matzinger [7] published her famous danger hypothesis which was remarkably in line with our clinical observations. These clinical observations derived from a prospective, randomized double-blind placebo controlled clinical trial that showed a beneficial effect of human recombinant superoxide-dismutase (SOD) on acute and chronic rejection events in kidney-transplanted patients [4] . The principal design of this clinical study in recipients under cyclosporine-based immunosupHartmann G, Wagner H (eds): Innate Immunity: Resistance and Disease-Promoting Principles. Else Kröner-Fresenius Symp. Basel, Karger, 2013, vol 4, pp 24–28 (DOI: 10.1159/000346531) The Innate Immune System: Its Rediscovery before Toll Was Described Walter G. Land Konrad Messmer German Academy of Transplantation Medicine, Munich , Former Institute for Surgical Research, University of Munich, Munich , Germany Chapter 2: Innate Immunity and Transplantation D ow nl oa de d by : U B d er L M U M ün ch en 12 9. 18 7. 25 4. 47 1 0/ 20 /2 01 4 2: 41 :5 2 P M