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Curr Opin Immunol. 2004 Oct;16(5):550-7.

New spectrum of allorecognition pathways: implications for graft rejection and transplantation tolerance.

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  • 1Department of Immunology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, W120NN, UK.


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.

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