Interaction between lymph and liver cells may affect immune response

November 01, 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."
-end-
Article: "T Lymphocytes Interact With Hepatocytes Through Fenestrations in Murine Liver Sinusoidal Endothelial Cells," Alessandra Warren, David G. Le Couteur, Robin Fraser, David G. Bowen, Geoffrey W. McCaughan, Patrick Bertolino, Hepatology; November 2006 (DOI: 10.1002/hep.21378).

Editorial: "Holey Endothelium: Gateways for Naïve T Cell Activation," Erin F. McAvoy, Paul Kubes, Hepatology; November 2006 (DOI: 10.1002/hep.21421).

Wiley

Related Immune Response Articles from Brightsurf:

Boosting chickens' own immune response could curb disease
Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks.

Cells sacrifice themselves to boost immune response to viruses
Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection.

Children's immune response more effective against COVID-19
Children and adults exhibit distinct immune system responses to infection by the virus that causes COVID-19, a finding that helps explain why COVID-19 outcomes tend to be much worse in adults, researchers from Yale and Albert Einstein College of Medicine report Sept.

Which immune response could cause a vaccine against COVID-19?
Immune reactions caused by vaccination can help protect the organism, or sometimes may aggravate the condition.

Obesity may alter immune system response to COVID-19
Obesity may cause a hyperactive immune system response to COVID-19 infection that makes it difficult to fight off the virus, according to a new manuscript published in the Endocrine Society's journal, Endocrinology.

Immune response to Sars-Cov-2 following organ transplantation
Even patients with suppressed immune systems can achieve a strong immune response to Sars-Cov-2.

'Relaxed' T cells critical to immune response
Rice University researchers model the role of relaxation time as T cells bind to invaders or imposters, and how their ability to differentiate between the two triggers the body's immune system.

A novel mechanism that triggers a cellular immune response
Researchers at Baylor College of Medicine present comprehensive evidence that supports a novel trigger for a cell-mediated response and propose a mechanism for its action.

Platelets exacerbate immune response
Platelets not only play a key role in blood clotting, but can also significantly intensify inflammatory processes.

How to boost immune response to vaccines in older people
Identifying interventions that improve vaccine efficacy in older persons is vital to deliver healthy ageing for an ageing population.

Read More: Immune Response News and Immune Response Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.