title: Graft rejection - endogenous or allogeneic?
abstract: The presence and persistence of alloantigen is necessary for graft-specific T-cell-mediated immunity. However, specificity comprises only a single facet of an extremely complex process. Evidence is accruing to suggest that immunogenicity could be manipulated by endogenous ligands released during tissue injury. Stress molecules are significantly up-regulated following transplantation and stimulate conserved receptors on a range of leucocytes, including dendritic cells (DCs). The DCs are essential for co-stimulation and the induction of adaptive immunity. Stress signals can act as an adjuvant leading to DC maturation and activation. DCs stimulated by endogens exhibit enhanced alloantigen presentation, co-stimulation and production of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18. Inflammasomes have a major role in IL-1β/IL-18 production and secretion, and can be stimulated by endogens. Importantly, the polarization toward inflammatory T helper type 17 cells as opposed to regulatory T cells is dependent upon, among other factors, IL-1β. This highlights an important differentiation pathway that may be influenced by endogenous signals. Minimizing graft damage and stress expression should hypothetically be advantageous, and we feel that this area warrants further research, and may provide novel treatment modalities with potential clinical benefit.
authors.affiliation: The Transplant Centre, University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital, The University of Manchester, Manchester, UK.
authors.forename: William R
authors.initials: WR
authors.lastname: Critchley
authors.forename: James E
authors.initials: JE
authors.lastname: Fildes
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D051381:Rats; D013312:Stress, Physiological / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000941:Antigens; D016207:Cytokines