Mechanisms of Rejection: Current Perspectives

Abstract

Rejection is the major barrier to successful transplantation. The immune response to an allograft is an ongoing dialogue between the innate and adaptive immune system that if left unchecked will lead to the rejection of transplanted cells, tissues, or organs. 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. T cells require a minimum of two signals for activation, antigen recognition, and costimulation. The activation requirements of naive T cells are more stringent than those of memory T cells. Memory T cells are present in the majority of transplant recipients as a result of heterologous immunity. The majority of B cells require help from T cells to initiate antibody production. Antibodies reactive to donor human leukocyte antigen molecules, minor histocompatibility antigens, endothelial cells, RBCs, or autoantigens can trigger or contribute to rejection early and late after transplantation. Antibody-mediated rejection triggered by alloantibody binding and complement activation is recognized increasingly as a significant contribution to graft loss. Even though one component of the immune system may dominate and lead to rejection being described in short hand as T cell or antibody mediated, it is usually multifactorial resulting from the integration of multiple mechanisms. Identifying the molecular pathways that trigger tissue injury, signal transduction and rejection facilitates the identification of targets for the development of immunosuppressive drugs.

Selective, efficient modulation of activated CD4+ αβT cells by the novel humanized antibody GZ-αβTCR targeting human αβTCR

“…[44][45][46] GZ-αβTCR-as we show-spared non-αβ immune effector cells, namely γδT cells, that are endowed with unique functional and antigen specificities, execute a broad spectrum of cell-cell interactions and have potent immune regulatory capacity. 47 Their continuance is of specific significance early after haematopoietic SCT when patients, still immunocompromised, suffer from a high risk of lymphoproliferative disorders 48 and relapse of the underlaying disease, as γδT cells can suppress B-cell expansion, 49 regulate T-cell leukaemia and exert potent antitumoural activity.…”

Innate Allorecognition Results in Rapid Accumulation of Monocyte-Derived Dendritic Cells

“…This is particularly important in the setting of organ transplantation, where allografts are subjected to immunological rejection through various mechanisms, including cell-and Ab-mediated processes (10). However, how the host innate immune system responds to allogeneic stimuli is not fully defined because transplantation procedures are generally performed under sterile conditions.…”

Association of Early Kidney Allograft Failure with Preformed IgA Antibodies to β 2-Glycoprotein I

“…6 However, other antibodies against minor histocompatibility antigens, endothelial cells, or autoantigens have also been recognized as harmful for renal allograft outcomes. [7][8][9] Antiphospholipid (aPL) antibodies are a group of autoantibodies against phospholipids, phospholipids binding proteins, or both that are localized on membranes of endothelial and other cells involved in the coagulation cascade. 10,11 Antibodies against phospholipids per se are associated with infectious diseases, whereas autoantibodies associated with vascular pathology are directed against b 2 -glycoprotein I (B2GPI), 12 a serum protein that is synthesized in the liver, bowel, and kidney.…”