The mechanisms of acute transplant rejection revisited.

For many years, acute rejection has been considered as a typical response of the adaptive immunity system. However, recent investigations have revealed a critical role for innate immunity as a pivotal trigger in adaptive immune responses. Danger signals released by cells damaged or killed by injury or disease may be intercepted by Toll-like receptors (TLRs) that alarm the dendritic cells (DCs) through the activation of transcription factors. In the presence of an inflammatory milieu created by other components of the innate immunity, DCs become mature and present the antigen to naïve T cells. The activation of T cells requires both a signal engendered by the presentation of the antigen to the T cell receptor and costimulatory signals generated by the contact between molecules displayed by antigen-presenting cells (APCs) and by T cells. Once activated, T cells encode and synthesize interleukin 2 (IL-2) and other cytokines that provide the signals for cell differentiation and proliferation. Until recently, little attention was paid to the role of antibodies in renal transplantation. However, there is mounting evidence that a number of kidney allografts fail as a consequence of a rejection caused by antibodies specifically directed against major histocompatibility complex antigens, class I or II, of the recipient. A critical role in antibody-mediated rejection (AMR) is played by complement. A number of therapeutic attempts have been tried to prevent or treat AMR. The still open question is whether the antibodies we detect are those responsible for tissue damage or not.