Mechanisms of Immune Tolerance in Liver Transplantation-Crosstalk Between Alloreactive T Cells and Liver Cells With Therapeutic Prospects

Liver transplantation (LTx) is currently the most powerful treatment for end-stage liver disease. Although liver allograft is more tolerogenic compared to other solid organs, the majority of LTx recipients still require long-term immune suppression (IS) to control the undesired alloimmune responses, which can lead to severe side effects. Thus, understanding the mechanism of liver transplant tolerance and crosstalk between immune cells, especially alloreactive T cells and liver cells, can shed light on more specific tolerance induction strategies for future clinical translation. In this review, we focus on alloreactive T cell mediated immune responses and their crosstalk with liver sinusoidal endothelial cells (LSECs), hepatocytes, hepatic stellate cells (HSCs), and cholangiocytes in transplant setting. Liver cells mainly serve as antigen presenting cells (APCs) to T cells, but with low expression of co-stimulatory molecules. Crosstalk between them largely depends on the different expression of adhesion molecules and chemokine receptors. Inflammatory cytokines secreted by immune cells further elaborate this crosstalk and regulate the fate of naïve T cells differentiation within the liver graft. On the other hand, regulatory T cells (Tregs) play an essential role in inducing and keeping immune tolerance in LTx. Tregs based adoptive cell therapy provides an excellent therapeutic option for clinical transplant tolerance induction. However, many questions regarding cell thera...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

Related Links:

AbstractLiver transplantation has become a definitive treatment for patients with end-stage liver disease and those meeting Milan criteria for hepatocellular carcinoma. The morbidity and mortality associated with liver transplantation continues to decrease thanks to refinements in surgical technique, immunosuppression, and imaging. In particular, imaging plays a vital role by facilitating early detection of post-operative complications and enabling prompt treatment. Post-operative complications that lead to graft failure and patient morbidity/mortality can be generally categorized as vascular, biliary, parenchymal, and mal...
Source: Abdominal Imaging - Category: Radiology Source Type: research
Carriers of telomerase related genes (TRG) mutation seem to present a worst prognosis with more common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT and identify pre-LT prognosis factors in a multicenter cohort of lung transplant recipients with TRG mutation.We retrospectively reviewed all identified patients with pathogenic TRG mutation (n=38; TERT, n=22, TERC, n=10, RTEL1, n=6) who received LT in France, Switzerland and Belgium between 2009 and 2018. The median age at LT was 54 years (46-59), 70% were male, and 60% had idiop...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Transplantation Source Type: research
ConclusionWe identified important psychosocial predictors of post-LT alcohol relapse and validated SIPAT and SALT scores as pre-transplant risk factors for alcohol relapse.
Source: Digestive Diseases and Sciences - Category: Gastroenterology Source Type: research
“The intestinal transplantation is reserved for patients with life-threatening complications of permanent intestinal failure or underlying gastrointestinal disease. The choice of the allograft for a particular patient depends on several factors and the presence of concurrent organ failure, and ava ilability of the donor organs, and specialized care. Combined liver and intestinal transplant allows for patients who have parenteral nutrition–associated liver disease a possibility of improved quality of life and nutrition as well as survival. Intestinal transplantation has made giant strides ov er the past few deca...
Source: Gastroenterology Clinics of North America - Category: Gastroenterology Authors: Source Type: research
CONCLUSIONS Cyclosporine, Everolimus, and Belatacept suppressed the alloresponse of primary human hepatocytes in an MLHC without significant cytotoxicity or functional cell impairment. PMID: 31406101 [PubMed - in process]
Source: Annals of Transplantation - Category: Transplant Surgery Authors: Tags: Ann Transplant Source Type: research
DR JASON WELLEN (St Louis, MO): Dr Cannon and colleagues have presented a retrospective analysis of United Network for Organ Sharing (UNOS) data comparing the outcomes of kidney transplantation, after a simultaneous liver kidney transplantation (SLK), compared with a matched cohort of kidney transplants. They used UNOS data between 2003 and 2012 in order to incorporate the changes to the Model for End-Stage Liver Disease (MELD) allocation. Their manuscript sought to illustrate the potential lost life years of kidney allografts that are being transplanted as SLKs.
Source: Journal of the American College of Surgeons - Category: Surgery Tags: Western surgical association article Source Type: research
The use of extended criteria donors (ECD) in liver transplantation is increasing due to the organ shortage. Histological evaluation of the liver graft in the context of procurement is an important tool for extending the donor pool without affecting the quality of the transplanted organs. Macrovesicular steatosis is widely accepted as predictor of early allograft dysfunction (EAD), while other features, such as portal fibrosis, are poorly studied.
Source: Digestive and Liver Disease - Category: Gastroenterology Authors: Tags: Liver, Pancreas and Biliary Tract Source Type: research
Authors: Boyd A, Newsome P, Lu WY Abstract INTRODUCTION: Liver disease is an increasing cause of worldwide mortality, and currently the only curative treatment for end-stage liver disease is whole organ allograft transplantation. Whilst this is an effective treatment, there is a shortage of suitable grafts and consequently some patients die whilst on the waiting list. Cell therapy provides an alternative treatment to increase liver function and potentially ameliorate fibrosis. Areas covered: In this review we discuss the different cellular sources for therapy investigated to date in humans include mature hepatocyte...
Source: Expert Review of Gastroenterology and Hepatology - Category: Gastroenterology Tags: Expert Rev Gastroenterol Hepatol Source Type: research
ConclusionBy integrating both clinical and genetic variables, liver transplant recipients can be categorized into different risk groups, and might benefit from individualized therapies.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
Conclusions: While there is a certain overlap between the results of the current study and published transcriptomic profiles of non-transplanted livers with steatosis, we have identified discrete characteristics of the non-alcoholic fatty liver disease in liver grafts potentially utilizable for the establishment of predictive signature. Introduction Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries, its prevalence being estimated at 19–31.3% (1). It encompasses a range of conditions that are thought to arise from fatty liver (simple steatosis) throu...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
More News: Allergy & Immunology | Bone Graft | Clinical Trials | Liver | Liver Disease | Liver Transplant | Transplant Surgery | Transplants | Urology & Nephrology