Environmental peer pressure: CD4(+) T cell help in tolerance and transplantation

• Type of Material: Article
• Authors: Dana Tedesco, Emory University; Arash Grakoui, Emory University
• Language: English
• Date: 2018-01-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 by the American Association for the Study of Liver Diseases.
• Final Published Version (URL): http://dx.doi.org/10.1002/lt.24873
• Title of Journal or Parent Work: Liver Transplantation
• ISSN: 1527-6465
• Volume: 24
• Issue: 1
• Start Page: 89
• End Page: 97
• Grant/Funding Information: Supported by NIH grants R01AI070101, R01AI124680, and R01AI126890 to A.G., and ORIP/OD P51OD011132 (formerly NCRR P51RR000165) to the Yerkes National Primate Research Center.
• Keywords: DENDRITIC CELLS; LIVER-KIDNEY TRANSPLANTATION; SINUSOIDAL ENDOTHELIAL-CELLS; HEPATIC STELLATE CELLS; ISCHEMIA-REPERFUSION INJURY; Science & Technology; Life Sciences & Biomedicine; ANTIBODY-MEDIATED REJECTION; IMMUNOLOGICAL-TOLERANCE; LYMPHOCYTOTOXIC ALLOANTIBODIES; KUPFFER CELLS; Gastroenterology & Hepatology; Transplantation; Surgery; SINGLE-CENTER
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology

Abstract

The liver participates in a multitude of metabolic functions that are critical for sustaining human life. Despite constant encounters with antigenic-rich intestinal blood, oxidative stress, and metabolic intermediates, there is no appreciable immune response. Interestingly, patients undergoing orthotopic liver transplantation benefit from a high rate of graft acceptance in comparison to other solid organ transplant recipients. In fact, cotransplantation of a donor liver in tandem with a rejection-prone graft increases the likelihood of graft acceptance. A variety of players may account for this phenomenon including the interaction of intrahepatic antigen-presenting cells with CD4+ T cells and the preferential induction of forkhead box P3 (Foxp3) expression on CD4+ T cells following injurious stimuli. Ineffective insult management can cause chronic liver disease, which manifests systemically as the following: antibody-mediated disorders, ineffective antiviral and antibacterial immunity, and gastrointestinal disorders. These sequelae sharing the requirement of CD4+ T cell help to coordinate aberrant immune responses. In this review, we will focus on CD4+ T cell help due to the shared requirements in hepatic tolerance and coordination of extrahepatic immune responses. Overall, intrahepatic deviations from steady state can have deleterious systemic immune outcomes and highlight the liver's remarkable capacity to maintain a balance between tolerance and inflammatory response while simultaneously being inundated with a panoply of antigenic stimuli. Liver Transplantation 24 89–97 2018 AASLD.