TY - JOUR
T1 - Continuous Acquisition of MHC
T2 - Peptide Complexes by Recipient Cells Contributes to the Generation of Anti-Graft CD8+ T Cell Immunity
AU - Smyth, L. A.
AU - Lechler, R. I.
AU - Lombardi, G.
N1 - This article is protected by copyright. All rights reserved.
PY - 2017/1
Y1 - 2017/1
N2 - Understanding the evolution of the direct and indirect pathways of allorecognition following tissue transplantation is essential in the design of tolerance-promoting protocols. On the basis that donor bone marrow-derived antigen presenting cells are eliminated within days of transplantation, it has been argued that the indirect response represents the major threat to long term transplant survival, and is consequently the key target for regulation. However, the detection of MHC transfer between cells, and particularly the capture of MHC:peptide complexes by dendritic cells, led us to propose a third, semi-direct, pathway of MHC allorecognition. Persistence of this pathway would lead to sustained activation of direct pathway T cells, arguably persisting for the life of the transplant. In this study, we focused on the contribution of acquired MHC class I, on recipient DCs, during the life span of a skin graft. We observed that MHC class I acquisition by recipient DCs occurs for at least one month following transplantation and may be the main source of alloantigen that drives CD8(+) cytotoxic T cell responses. In addition, acquired MHC class I-peptide complexes stimulate T cell responses in vivo further emphasizing the need to regulate both pathways to induce indefinite survival of the graft. This article is protected by copyright. All rights reserved.
AB - Understanding the evolution of the direct and indirect pathways of allorecognition following tissue transplantation is essential in the design of tolerance-promoting protocols. On the basis that donor bone marrow-derived antigen presenting cells are eliminated within days of transplantation, it has been argued that the indirect response represents the major threat to long term transplant survival, and is consequently the key target for regulation. However, the detection of MHC transfer between cells, and particularly the capture of MHC:peptide complexes by dendritic cells, led us to propose a third, semi-direct, pathway of MHC allorecognition. Persistence of this pathway would lead to sustained activation of direct pathway T cells, arguably persisting for the life of the transplant. In this study, we focused on the contribution of acquired MHC class I, on recipient DCs, during the life span of a skin graft. We observed that MHC class I acquisition by recipient DCs occurs for at least one month following transplantation and may be the main source of alloantigen that drives CD8(+) cytotoxic T cell responses. In addition, acquired MHC class I-peptide complexes stimulate T cell responses in vivo further emphasizing the need to regulate both pathways to induce indefinite survival of the graft. This article is protected by copyright. All rights reserved.
U2 - 10.1111/ajt.13996
DO - 10.1111/ajt.13996
M3 - Article
C2 - 27495898
SN - 1600-6135
VL - 17
SP - 60
EP - 68
JO - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
JF - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
IS - 1
ER -
