Migration of allosensitizing donor myeloid dendritic cells into recipients after liver transplantation.
It is thought, but there is no evidence, that myeloid dendritic cells (MDCs) of donor origin migrate into the recipient after clinical organ transplantation and sensitize the recipient's immune system by the direct presentation of donor allo-antigens. Here we show prominent MDC chimerism in the recipient's circulation early after clinical liver transplantation (LTx) but not after renal transplantation (RTx). MDCs that detach from human liver grafts produce large amounts of pro-inflammatory [tumor necrosis factor alpha and interleukin 6 (IL-6)] and anti-inflammatory (IL-10) cytokines upon activation with various stimuli, express higher levels of toll-like receptor 4 than blood or splenic MDCs, and are sensitive to stimulation with a physiological concentration of lipopolysaccharide (LPS). Upon stimulation with LPS, MDCs detaching from liver grafts prime allogeneic T cell proliferation and production of interferon gamma but not of IL-10. Soluble factors secreted by liver graft MDCs amplify allogeneic T helper 1 responses. In conclusion, after clinical LTx, but not after RTx, prominent numbers of donor-derived MDCs migrate into the recipient's circulation. MDCs detaching from liver grafts produce pro-inflammatory and anti-inflammatory cytokines and are capable of stimulating allogeneic T helper 1 responses, and this suggests that MDC chimerism after clinical LTx may contribute to liver graft rejection rather than acceptance.
Department of Gastroenterology and Hepatology, University Medical Center, Rotterdam, the Netherlands.
Brenda M
BM
Bosma
Herold J
HJ
Metselaar
Jeroen H
JH
Gerrits
Nicole M
NM
van Besouw
Shanta
S
Mancham
Zwier M A
ZM
Groothuismink
Patrick P C
PP
Boor
Luc J W
LJ
van der Laan
Hugo W
HW
Tilanus
Ernst J
EJ
Kuipers
Jaap
J
Kwekkeboom
D002465:Cell Movement; D046528:Chimerism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation; D008070:Lipopolysaccharides; D016031:Liver Transplantation; D018417:Th1 Cells / Q000502:physiology; D023001:Transplantation Tolerance
D016207:Cytokines; D008070:Lipopolysaccharides