title: Effector mechanisms in transplant rejection.
abstract: Antigens, provided by the allograft, trigger the activation and proliferation of allospecific T cells. As a consequence of this response, effector elements are generated that mediate graft injury and are responsible for the clinical manifestations of allograft rejection. Donor-specific CD8+ cytotoxic T lymphocytes play a major role in this process. Likewise, CD4+ T cells mediate delayed-type hypersensitivity responses via the production of soluble mediators that function to further activate and guide immune cells to the site of injury. In addition, these mediators may directly alter graft function by modulating vascular tone and permeability or by promoting platelet aggregation. Allospecific CD4+ T cells also promote B-cell maturation and differentiation into antibody-secreting plasma cells via CD40-CD40 ligand interactions. Alloantibodies that are produced by these B cells exert most of their detrimental effects on the graft by activating the complement cascade. Alternatively, antibodies can bind Fc receptors on natural killer cells or macrophages and cause target cell lysis via antibody-dependent cell-mediated cytotoxicity. In this review, we discuss these major effector pathways, focusing on their role in the pathogenesis of allograft rejection.
authors: Duke University and Durham VA Medical Centers, Durham, NC 27705, USA.
authors: Paulo N
authors: PN
authors: Rocha
authors: Troy J
authors: TJ
authors: Plumb
authors: Steven D
authors: SD
authors: Crowley
authors: Thomas M
authors: TM
authors: Coffman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D015289:Leukotrienes; D011453:Prostaglandins