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 To proliferate or not to proliferate
21.03.2019 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Discovery of a Primordial Metabolism in Microbes
21.03.2019 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

Im Focus: Revealing the secret of the vacuum for the first time

New research group at the University of Jena combines theory and experiment to demonstrate for the first time certain physical processes in a quantum vacuum

For most people, a vacuum is an empty space. Quantum physics, on the other hand, assumes that even in this lowest-energy state, particles and antiparticles...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

To proliferate or not to proliferate

21.03.2019 | Life Sciences

Magnetic micro-boats

21.03.2019 | Physics and Astronomy

Motorless pumps and self-regulating valves made from ultrathin film

21.03.2019 | HANNOVER MESSE

VideoLinks
Science & Research
Overview of more VideoLinks >>>