Navigation Links
Interaction between lymph and liver cells may affect immune response

A new study on the ability of liver cells to interact with T cells (lymph cells that play a role in regulating the immune response) found that such interactions do occur and demonstrated the mechanism by which they may take place. The results may help explain the altered immune responses that occur with aging and other conditions and may be useful in developing therapies for viral hepatitis and autoimmune diseases.

The results of this study appear in the November 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.

The liver possesses an unusual ability to stimulate immune tolerance, possibly due to its distinctive architecture that allows T cells normally activated in the lymph system to become activated by liver cells. Normally, endothelial cells that line blood vessels form a physical barrier that prevents naïve (unactivated) T cells from accessing surrounding tissue; these cells must typically be activated by specialized cells known as professional antigen presenting cells (APCs) before they are able to migrate across the endothelium and interact with organ cells. Recent studies have shown that the liver is an exception in that liver cells may be able to act as APCs, activating T cells independently of the lymph system, a process which makes them less efficient. However, the question remains as to how T cells can cross the endothelial barrier to interact with liver cells.

A collaborative work between Alessandra Warren and David Le Couteur of the Centre for Education and Research on Ageing (CERA), Concord RG Hospital and Patrick Bertolino of the Centenary Institute, University of Sydney, Australia, has led to the first study investigating the interactions b etween lymphocytes (T cells), liver sinusoidal endothelial cells (LSECs) and hepatocytes (liver cells) using electron microscopy. LSECs are highly specialized endothelial cells that line the walls of hepatic sinusoid cells (gossamer-like structures that form the rich capillary network of the liver) and are perforated by fenestrations, or openings. The researchers hypothesized that the fenestrations could provide a portal through which liver cells and T cells could interact or that the interaction could take place across gaps between LSECs.

The study was conducted using mice whose livers had been injected with lymphocytes. The mouse livers were examined with two types of electron microscopy. Analysis of the images showed a large number of intrahepatic lymphocytes (IHLs) that had extensions similar to the dimensions of the fenestrations of the LSECs. These extensions were seen within the fenestrations and were observed to be in contact with minute projections on liver cells (hepatocyte microvilli). There were no observable gaps between LSECs and hepatocyte microvilli did not seem to interact with circulating lymphocytes. Further investigation showed that naïve T cells displayed the same extensions as IHLs and were also able to interact with liver cells through LSEC fenestrations. The authors propose the term "trans-endothelial hepatocyte-lymphocyte interactions" (TEHLI) to describe these interactions.

The discovery of TEHLI is the first demonstration by electron microscopy of the interaction between naïve T cells and liver cells in a living organism, which shows that the liver is an exception to the rule that T cells need to be activated by professional APCs in order to cross the endothelial barrier, and that hepatocytes can function as APCs. In fact, this T cell activation in the liver during early hepatitis C infection may contribute to the impaired immune response seen in chronic hepatitis C.

"As well as providing insight into the norm al immune system, our observations might have implications for liver conditions associated with altered LSEC morphology and in particular those conditions associated with loss of fenestrations such as cirrhosis and old age," the authors conclude. "We have shown [in previous studies] that old age is associated with dramatic reductions in the fenestrations of LSECs therefore the altered immune responses of older people might in part be mechanistically linked to reduced opportunity for TEHLI in old age."

In an accompanying editorial in the same issue, Erin F. McAvoy and Paul Kubes of the University of Calgary in Alberta, Canada note that although the authors did not observe any interaction between hepatocyte microvilli and circulating lymphocytes, it is possible that this type of transient interaction is difficult to capture using electron microscopy. They suggest that the hepatocyte microvilli could function as a rapid screen for circulating lymphocytes, which might then decide to adhere and start the TEHLI process. "The notion that naïve T lymphocytes are capable of directly interacting with hepatocytes contradicts the dogma that naïve T cells cannot gain access to peripheral non-lymphoid tissues," the authors state, adding that the study furthers the notion that liver cells may be involved in hepatic immune tolerance. "Like any good study," they conclude, "the work of Warren et al., answers important questions but also raises some new and intriguing areas for further exploration."
'"/>

Source:John Wiley & Sons, Inc.


Related biology news :

1. Variation in womens X chromosomes may explain differences among individuals, between sexes
2. Edible bivalves as a source of human pathogens: signals between vibrios and the bivalve host.
3. Study reveals dramatic difference between breast cancers in US and Africa
4. Molecular fossils uncover link between viruses and the immune system
5. Research may provide new link between soft drinks and weight gain
6. A new molecule discovered in the battle between plants and disease
7. Underground tunnels discovered as means for communication between immune system cells
8. New discovery blurs distinction between human cells and those of bacteria
9. Plants discriminate between self and non self
10. Genetic link confirmed between Polynesians and indigenous Taiwanese
11. European Commission funds EBI to do new research on synergies between bioinformatics and medical informatics

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:11/24/2016)... -- Cercacor today introduced Ember TM Sport Premium ... measure hemoglobin, Oxygen Content, Oxygen Saturation, Perfusion Index, ... approximately 30 seconds. Smaller than a smartphone, using only ... key data about their bodies to help monitor these ... Hemoglobin carries oxygen to muscles. When hemoglobin and ...
(Date:11/19/2016)... Securus Technologies, a leading provider of civil ... corrections and monitoring, announced today that it has offered ... an independent technology judge determine who has the largest ... telephone calling platform, and the best customer service. ... of what we do – which clearly is not ...
(Date:11/15/2016)... ROCKVILLE, Md. , Nov. 15, 2016 /PRNewswire/ ... clinical company developing therapeutics focused on the gut ... public offering of 25,000,000 shares of its common ... its common stock at a price to the ... gross proceeds to Synthetic Biologics from the offering, ...
Breaking Biology News(10 mins):
(Date:12/2/2016)... (PRWEB) , ... December 02, ... ... (ETC), a consortium of pharmaceutical and biotechnology companies dedicated to collaboratively developing ... companies interested in supplying a vendor-supported, portable online UHPLC, with robust, probe-based ...
(Date:12/2/2016)... , December 2, 2016 The ... 2021, growing at a CAGR of 7.3% during the forecast period ... hospitals and diagnostic laboratories segment accounted for the largest share of ... ... report on global immunohistochemistry (IHC) market spread across 225 pages, profiling ...
(Date:11/30/2016)... 30, 2016  GenomOncology today announced the appointment of ... Affairs.  Dr. Coleman will oversee clinical content ... knowledge-enabled platform. The GenomOncology software suite empowers molecular pathologists with ... and clinical decision support, from quality control through reporting. ... , , ...
(Date:11/30/2016)... 2016 Biotest Pharmaceuticals Corporation (BPC), a leading ... the addition of its newest plasma collection center located ... . The 15,200 square foot state-of-the-art facility officially opened ... brings the total number of BPC,s plasma collection centers ... BPC,s Chief Executive Officer said "We are pleased to ...
Breaking Biology Technology: