title: New spectrum of allorecognition pathways: implications for graft rejection and transplantation tolerance.
abstract: It has long been appreciated that MHC alloantigens can be recognized via two pathways; direct and indirect. The relative contributions of these two pathways to transplant rejection are partially understood. In studies of transplantation tolerance it appears that regulatory T cells (Trs) with indirect allospecificity, particularly the CD4+CD25+ population, play a key role and can regulate responder cells with direct allospecificity for the same alloantigens. One of the conundrums that remains is how helper T and Tr cells with indirect allospecificity regulate T cells with direct allospecificity. At face value, this appears to break the rules of linkage that require interacting T cells to make contact with the same antigen-presenting cell. A third, 'semi-direct' pathway involving MHC exchange may help to resolve this conundrum. Insights into how these pathways interact in transplant immunity and tolerance will assist the pursuit of clinical tolerance.
authors.affiliation: Department of Immunology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, W120NN, UK. sjiang@imperial.ac.uk
authors.forename: Shuiping
authors.initials: S
authors.lastname: Jiang
authors.forename: Osquel
authors.initials: O
authors.lastname: Herrera
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous