Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Interaction between lymph and liver cells may affect immune response

03.11.2006
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 between 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 normal 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."

David Greenberg | EurekAlert!
Further information:
http://www.interscience.wiley.com/journal/hepatology

More articles from Life Sciences:

nachricht Ambush in a petri dish
24.11.2017 | Friedrich-Schiller-Universität Jena

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>