Locally produced complement and its role in renal allograft rejection

The role of innate immunity in allograft injury is just beginning to become clear, and complement is probably one of a number of factors that are activated very early in the course of transplantation. Kidney transplantation into complement-inhibited rats reduces subsequent inflammation of the graft, probably as a result of reduction of ischemia reperfusion damage as well as diminution of immune mediated damage. Closer analysis of the role of locally synthesised components in mice has suggested that regional synthesis of complement proteins, in particular by the renal tubule, may play a more important role than circulating components. A marked effect on the antidonor T cell response may be explained by the triggering of complement receptors present on antigen presenting cells or T cells infiltrating the graft, or by a more direct effect of complement on the liaison between proximal tubule cells and T cells. Therapeutic control is likely to require a shift to a more targeted approach, directed at complement components produced in the extravascullar tissue compartment.