Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Notch protein signaling directs early T-cell development

07.07.2005


A better grasp of immune cell lineages may improve outcomes for transplant, other immunosuppressed patients



Researchers at the University of Pennsylvania School of Medicine have recently clarified the role of the Notch protein in T-cell development. T cells are required for many aspects of immunity, including fighting viral infections, providing cancer surveillance, and regulating multiple aspects of the immune response.

T cells are made in the thymus, a small organ situated under the breastbone near the heart, whose primary function is T-cell production. However, T cells ultimately come from hematopoietic (blood-producing) stem cells in the bone marrow, from which all blood-cell types begin. A progenitor cell leaves the bone marrow to seed the thymus, eventually giving rise to T cells. In the absence of instructions by the Notch protein, T-cell development does not occur, even in the presence of a normal thymus.


In this study–published in the most recent issue of Nature Immunology–the investigators found that Notch, a protein that regulates diverse cell-fate decisions in multi-cellular organisms, is active in very early T-cell progenitors in the thymus of mice. Notch contributes to the subsequent differentiation of these early T-cell progenitors into T cells.

"Notch signaling instructs multi-potent progenitor cell types to enter the T-cell developmental pathway," says senior author Avinash Bhandoola, MD, PhD, Assistant Professor of Pathology and Laboratory Medicine. "However, we don’t yet understand in which tissue these instructions are being delivered, and which cell type is the recipient."

Co-author Warren Pear, MD, PhD, Associate Professor of Pathology and Lab Medicine and member of Penn’s Abramson Family Cancer Research Institute and Institute for Medicine and Engineering, was one of the original discoverers of the role of Notch in T-cell development. His lab developed tools to block Notch signaling, which were key to identifying its function in T-cell progenitors. Findings from this current study suggest that Notch acts very early after progenitor cells enter the thymus, among other probable points in T-cell development.

Notch activates gene transcription in the nucleus of cells, and depending on the biochemical context, it turns certain pathways on, and others off. "To the extent that we know where, and in which cells Notch is acting, we may be able to figure out how Notch works in the thymus," says co-lead author Arivazhagan Sambandam, PhD, Research Associate, also in the Department of Pathology and Laboratory Medicine.

"Studying events in the thymus is important because intrathymic events may be a bottleneck in T-cell reconstitution, which is deficient in post-transplant patients," says co-lead author Ivan Maillard, MD, PhD, Research Associate in the Division of Hematology-Oncology and the Abramson Family Cancer Research Institute. "What the study allows us to do is begin to define exactly where intrathymic Notch signaling happens and where to look for problems and for the relevant molecular interactions."

In many clinical situations, early T-cell progenitors are likely to be deficient–especially in patients undergoing bone marrow or hematopoietic stem cell transplantation, in whom new T cells fail to be produced for long periods of time. In some, especially elderly patients, there is never true recovery of T cells, and such non-recovery is associated with problems such as infections. To improve the outcome of transplant patients, the process of T-cell development needs to be better understood. This may also be important in cancer patients who get profound immunosuppression from treatments and in AIDS patients when T cells are not made at a sufficient rate to replenish the T-cell pool.

The Pear and Bhandoola labs plan to apply the knowledge gained in their basic scientific studies to the clinic. According to Maillard, "In humans, it’s more difficult to look inside the thymus, but we plan to use our unique Notch reagents in model systems to generate hypotheses about the exact nature of Notch control of T-cell development, eventually moving that knowledge to relevant clinical situations."

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>