Abstract
T cells play an important role to build up an effective immune response and are essential in the eradication of pathogens. To establish a long-lasting protection even after a re-challenge with the same pathogen, some T cells differentiate into memory T cells. Recently, a certain subpopulation of memory T cells at different tissue-sites of infection was detected—tissue-resident memory T cells (TRM cells). These cells can patrol in the tissue in order to encounter their cognate antigen to establish an effective protection against secondary infection. The liver as an immunogenic organ is exposed to a variety of pathogens entering the liver through the systemic blood circulation or via the portal vein from the gut. It could be shown that intrahepatic TRM cells can reside within the liver tissue for several years. Interestingly, hepatic TRM cell differentiation requires a distinct cytokine milieu. In addition, TRM cells express specific surface markers and transcription factors, which allow their identification delimited from their circulating counterparts. It could be demonstrated that liver TRM cells play a particular role in many liver diseases such as hepatitis B and C infection, non-alcoholic fatty liver disease and even play a role in the development of hepatocellular carcinoma and in building long-lasting immune responses after vaccination. A better understanding of intrahepatic TRM cells is critical to understand the pathophysiology of many liver diseases and to identify new potential drug targets for the development of novel treatment strategies.
Highlights
Tcells play a central role in the immune response against pathogens
The rather recent identification of TRM cells as a distinct tissue-resident memory T cell subpopulation leads to the question: Which specific factors are involved in their development and maintenance, and which are crucial for their tissue-specific function?
Especially liver tissue, can just be obtained from living individuals most often suffering from end-stage liver disease and is limited to invasive tissue sampling through surgical resection, biopsy or more recently fine needle aspirates (FNA)
Summary
Tcells play a central role in the immune response against pathogens. CD8+ T cells are highly effective in the eradication of cells infected with pathogens, damaged cells and even cancer cells. A very important characteristic of the adaptive immune system is to build up a pool of memory T cells, which enables a fast and effective immune response after pathogen re-challenge These memory T cells patrol in the circulation in order to encounter a known pathogen. Different scientists were able to detect a persistent tissue-resident memory CD8 and CD4 T cell subpopulation at different tissue sites These cells can be mainly found in organs that are frequently exposed to pathogens, such as the liver, skin, gut and lung [1]. These resident memory T cells (TRM cells) are known to be important for pathogen surveillance in the respective tissue and have a distinct phenotype in comparison to their circulating counterparts in the blood [2,3]. In order to prevent a systemic infection, the liver plays an important role as a gatekeeper and an effective TRM cell population contributes to effective pathogen clearance
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