Liver Sinusoidal Endothelial Cells That Endocytose Allogeneic Cells Suppress T Cells with Indirect Allospecificity

Tokita, Daisuke; Shishida, Masayuki; Ohdan, Hideki; Onoe, Takashi; Hara, Hidetaka; Tanaka, Yuka; Ishiyama, K.; Mitsuta, Hiroshi; Ide, Kentaro; Arihiro, Koji; Asahara, Toshimasa

doi:10.4049/jimmunol.177.6.3615

Cited by 40 publications

(30 citation statements)

References 59 publications

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“…The LSECs that endocytosed the splenocytes showed enhanced expression of MHC class II molecules and CD80 (78). Of note, the notion that LSECs are capable of endocytosing/phagocytosing splenocytes is in contrast to the general concept that the cells under normal conditions do not take up material exceeding ϳ0.23 m (69).…”

Section: The Confusing Role Of Lsecs In Immunitymentioning

confidence: 96%

The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity

Elvevold

Smedsrød

Martínez³

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

213

212

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A look through the literature on liver sinusoidal endothelial cells (LSECs) reveals that there are several conflicts among different authors of what this cell type is and does. Major controversies that will be highlighted in this review include aspects of the physiological role, the characterization, and the protocols of isolation and cultivation of these cells. Many of these conflicts may be ascribed to the fact that the cell was only recently established as a distinct cell type and that researchers from different disciplines tend to define their structure and function differently. This field is in need of a common platform to obtain a sound communication and a unified understanding of how to interpret novel research results. The aim of this review is to encourage scientists not to ignore the fact that there are, indeed, different opinions in the literature on LSECs. We also hope that this review will point out to the reader that some issues that may seem well established regarding our knowledge about the LSECs, in reality, are still unresolved and, indeed, controversial.

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Section: The Confusing Role Of Lsecs In Immunitymentioning

confidence: 96%

The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity

Elvevold

Smedsrød

Martínez³

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

213

212

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“…10 Additionally, the attempts by portal injection of donor antigen usually led to donor-specific immune tolerance or prolonged graft survival. 11 The PV drained pancreas allografts displayed immunological benefits, revealed less rejection episodes, and better transplant outcome than the systemically drained grafts. 12 It was assumed that the antigen shedding from the graft will be delivered to the liver, which initiates the immune regulatory effects and mitigates the alloimmune response.…”

Section: Discussionmentioning

confidence: 99%

A novel model of portal vein transplantation in mice using two‐cuff technique

et al. 2007

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Allogeneic portal vein (PV) grafts have been widely used for vascular reconstruction in the aggressive biliary-pancreatic surgery and partial liver transplantation. We developed a novel PV transplantation model aimed at studying the pathologic alteration of the grafts and further managements. The PV graft was implanted orthotopically into the recipient using two-cuff technique. A total of 80 PV transplants have been performed, and the overall survival rate for the recipients was 91.3% (73/80). Mice were randomly separated into isografts group, allografts group, and allografts group treated with CTLA4-Ig. PV grafts were harvested on the 1st, 2nd, 4th, and 8th postoperative week. The isografts remained intact vascular structure, and the allografts developed marked rejection with significant increase in wall thickness (95 +/- 19 microm vs. 49 +/- 7 microm; P < 0.01) and decrease in lumen area (1.9 +/- 1.1 x 10(4) microm(2) vs. 7.7 +/- 3.1 x 10(4) microm(2); P < 0.01) on the 4th week. In the CTLA4-Ig treated group, the vascular thickness and lumen area were significantly improved when compared with the untreated allografts (wall-thickness: 53 +/- 3 microm vs. 95 +/- 19 microm, P < 0.01; lumen area: 8.8 +/- 2.4 x 10(4) microm(2) vs. 1.9 +/- 1.1 x 10(4) microm(2), P < 0.01) on the 4th week. In conclusion, the PV transplantation model in mice using two-cuff technique is a feasible procedure with a high survival rate. The PV allografts responded well to the CTLA4-Ig therapy in our preliminary research by the model.

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“…Furthermore, immunosuppression has successfully been withdrawn in some liver transplant recipients without detectable clinical consequences 5,6 . Exposure of antigens to the portal circulation or the hepatic immune locale may promote a tolerogenic response, which is shared with a few other immune compartments (i.e., anterior chamber of the eye, testis) 7–9 . Examples include the phenomena of portal venous tolerance, oral tolerance, spontaneous acceptance of whole liver allografts, and the persistent nature of hepatotropic viruses 10–12 .…”

Section: Introductionmentioning

confidence: 99%

Unique CD8+ T Cell–Mediated Immune Responses Primed in the Liver

et al. 2016

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Background The liver immune environment is tightly regulated to balance immune activation with immune tolerance. Understanding the dominant immune pathways initiated in the liver is important since the liver is a site for cell transplantation, such as for islet and hepatocyte transplantation. The purpose of this study is to examine the consequences of alloimmune stimulation when allogeneic cells are transplanted to the liver in comparison to a different immune locale, such as the kidney. Methods We investigated cellular and humoral immune responses when allogeneic hepatocytes are transplanted directly to the recipient liver by intraportal injection. A heterotopic kidney engraftment site was used for comparison to immune activation in the liver microenvironment. Results Transplantation of allogeneic hepatocytes delivered directly to the liver, via recipient portal circulation, stimulated long-term, high magnitude CD8+ T cell-mediated allocytotoxicity. CD8+ T cells initiated significant in vivo allocytotoxicity as well as rapid rejection of hepatocytes transplanted to the liver even in the absence of secondary lymph nodes or CD4+ T cells. In contrast, in the absence of recipient peripheral lymphoid tissue and CD4+ T cells, CD8-mediated in vivo allocytotoxicity was abrogated and rejection was delayed when hepatocellular allografts were transplanted to the kidney subcapsular site. Conclusions These results highlight the CD8-dominant proinflammatory immune responses unique to the liver microenvironment. Allogeneic cells transplanted directly to the liver do not enjoy immune privilege but rather require immunosuppression to prevent rejection by a robust and persistent CD8‐dependent allocytotoxicity primed in the liver.

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Liver Sinusoidal Endothelial Cells That Endocytose Allogeneic Cells Suppress T Cells with Indirect Allospecificity

Cited by 40 publications

References 59 publications

The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity

The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity

A novel model of portal vein transplantation in mice using two‐cuff technique

Unique CD8+ T Cell–Mediated Immune Responses Primed in the Liver

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