IFN-gamma, produced by NK cells that infiltrate liver allografts early after transplantation, links the innate and adaptive immune responses.
The role of NK cells following solid organ transplantation remains unclear. We examined NK cells in acute allograft rejection using a high responder model (DA-->Lewis) of rat orthotopic liver transplantation. Recipient-derived NK cells infiltrated liver allografts early after transplantation. Since chemokines are important in the trafficking of cells to areas of inflammation, we determined the intragraft expression of chemokines known to attract NK cells. CCL3 was significantly increased in allografts at 6 h post-transplant as compared to syngeneic grafts whereas CCL2 and CXCL10 were elevated in both syngeneic and allogeneic grafts. CXCL10 and CX3CL1 were significantly upregulated in allografts by day 3 post-transplant as compared to syngeneic grafts suggesting a role for these chemokines in the recruitment of effector cells to allografts. Graft-infiltrating NK cells were shown to be a major source of IFN-gamma, and IFN-gamma levels in the serum were markedly increased, specifically in allograft recipients, by day 3 post-transplant. Accordingly, in the absence of NK cells the levels of IFN-gamma were significantly decreased. Furthermore, graft survival was significantly prolonged. These data suggest that IFN-gamma-producing NK cells are an important link between the innate and adaptive immune responses early after transplantation.
Obara
Hideaki
H
Division of Transplantation Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California 94305-5492, USA.
Nagasaki
Kazuhito
K
Hsieh
Christine L
CL
Ogura
Yasuhiro
Y
Esquivel
Carlos O
CO
Martinez
Olivia M
OM
Krams
Sheri M
SM
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054428:Chemokine CX3CL1; D054357:Chemokine CXCL10; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000096:biosynthesis; D020523:Chemokines, CX3C / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003720:Densitometry; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006084:Graft Rejection; D007107:Immune System; D007113:Immunity, Innate; D007249:Inflammation; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D016031:Liver Transplantation / Q000379:methods*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D011917:Rats, Inbred Lew; D012260:Ribonucleases / Q000378:metabolism; D013997:Time Factors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
C496534:Ccl3 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054428:Chemokine CX3CL1; D054357:Chemokine CXCL10; D018925:Chemokines; D019742:Chemokines, CC; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; C515539:Cx3cl1 protein, mouse; C515540:Cx3cl1 protein, rat; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D008565:Membrane Proteins; D007371:Interferon-gamma; D012260:Ribonucleases