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

S Jiang, O Herrera, RI Lechler - Current opinion in immunology, 2004 - Elsevier
S Jiang, O Herrera, RI Lechler
Current opinion in immunology, 2004Elsevier
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 …
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.
Elsevier