Immune Responses to Tissue-Restricted Nonmajor Histocompatibility Complex Antigens in Allograft Rejection

Chronic diseases that result in end-stage organ damage cause inflammation,which can reveal sequestered self-antigens (sags) in that organ and trigger autoimmunity. the thymus gland deletes self-reactive t-cells against ubiquitously expressed sags,while regulatory mechanisms in the periphery control immune responses to tissue-restricted sags. it is now established that t-cells reactive to sags present in certain organs (e.g.,lungs,pancreas,and intestine) are incompletely eliminated,and the dysregulation of peripheral immuneregulation can generate immune responses to sags. therefore,chronic diseases can activate self-reactive lymphocytes,inducing tissue-restricted autoimmunity. during organ transplantation,donor lymphocytes are tested against recipient serum (i.e.,cross-matching) to detect antibodies (abs) against donor human leukocyte antigens,which has been shown to reduce ab-mediated hyperacute rejection. however,primary allograft dysfunction and rejection still occur frequently. because donor lymphocytes do not express tissue-restricted sags,preexisting abs against sags are undetectable during conventional cross-matching. preexisting and de novo immune responses to tissue-restricted sags (i.e.,autoimmunity) play a major role in rejection. in this review,we discuss the evidence that supports autoimmunity as a contributor to rejection. testing for preexisting and de novo immune responses to tissue-restricted sags and treatment based on immune responses after organ transplantation may improve short-and long-term outcomes after transplantation. � 2017 ankit bharat and t. mohanakumar.