Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Color-coded tracking method helps scientists analyze outcomes of newly transplanted tissue

28.05.2010
Novel imaging system paints a clear picture of T-cell actions in animal models, providing key insights into immune responses

A group of "color-coded" laboratory mice are providing researchers with a novel way of tracking T-cells, enabling them to visualize and monitor the cellular immune responses of transplanted tissue in real time. The new imaging system is described in the June issue of Nature Medicine, which appears on-line this week.

"These immune responses are a key consideration in developing strategies to improve transplant outcomes," explains co-senior author Terry Strom, MD, Co-director of the Transplant Institute at Beth Israel Deaconess Medical Center (BIDMC) and Professor of Medicine at Harvard Medical School (HMS). "The fate of a transplant following withdrawl of immunosuppressive therapy – either rejection or tolerance – is thought to be dependent upon the balance of destructive and protective T cells. With this new system, we can actually visualize this balance."

The acquisition of tolerance – a state in which transplanted tissue is not rejected by the body even in the absence of immunosuppressive therapy – is dependent upon several subsets of T cells, including protective regulatory T cells (Tregs) and destructive effector T cells (Teffs).

"The issue of whether newly transplanted tissue is attacked or protected is not a black-and-white situation," explains Strom. "Even when transplants are rejected, there will be some protective Treg cells present. And, conversely, in cases of tolerance – when the new transplant is accepted – there will still be some aggressive Teff cells at the scene of the crime." But, because it has not been possible for scientists to readily distinguish these two T cell subsets in vivo, the relative importance of these different types of T cells in the induction and maintenance of transplant tolerance has been unclear.

To address this issue, the BIDMC transplant immunology team, led by Strom and Maria Koulmanda, PhD, Associate Professor of Surgery at HMS, first created two mouse models – one that would express natural Treg cells (nTreg) in a fluorescent green protein and another in which Teff cells express a fluorescent red protein. (A third color, yellow, also came into play when the red effector T cells commit to the induced Treg phenotype, expressing both red and green fluorescent proteins and thereby appearing as yellow cells. This approach enables ready distinction between natural and induced Treg cells.)

The BIDMC investigators then partnered with a group of physicists at Massachusetts General Hospital led by Charles Lin, PhD. Lin and his team had developed a novel imaging technique that coupled in vivo flow cytometry with endoscopic confocal microscopy.

"Genetically mismatched insulin-producing islet cells were transplanted beneath the thin capsule surrounding the animals' kidneys," explains Koulmanda. "Infiltration of T cells into the transplant was then visualized in untreated recipient mice in which vigorous rejection occurred. These results were then compared with mice that had received a short course of treatment enabling them to permanently accept the transplant [i.e. immune tolerance]."

Using the new imaging process, the authors were able to clearly see that the ratio of protective T cells to destructive T cells differed markedly in the transplant tolerant mice compared with the mice in which transplant tissue was rejected. Among the "rejection mice," red cells rushed into the transplant far in advance of infiltration into the transplant by the tolerance hosts.

"As the events of rejection proceeded, the number of transplanted infiltrating T cells vastly exceeded those present in the tolerant transplants, even though the numbers of 'protective' yellow and green cells were equal in these groups at a later point in time," explains Koulmanda. "This is the first time that we have been able to monitor transplanted allograft tissue in a live lab animal. While static images of cells have been captured in the past, our new method captures much more than just random snapshots of the process."

"A picture really is worth a thousand words," adds Strom. "By enabling us to visualize this process, this new system has given us a clearer understanding of both quantitative and qualitative characteristics of the CD4 T cell response to allografts in rejecting and tolerized hosts. Fourteen days post-transplant, we were able to witness as costimulation blockade-based therapy inhibited infiltration by [the fluorescent red] Teff cells. Given the effectiveness of these tools, we hope to construct a road map such that we can create drug-free transplant tolerance for our patients in the future."

In addition to Strom, Koulmanda and Lin, coauthors include BIDMC investigators Zhigang Fan, Yan Lu, Gurbakhshish Singh and Vasilis Toxavidis; and MGH investigators Joel Spencer, Costas Pitsillides; Pilhan Kim and Seok Yun.

This study was supported, in part, by the National Institutes of Health and by the Juvenile Diabetes Research Foundation.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks in the top four in National Institutes of Health funding among independent hospitals nationwide. BIDMC is a clinical partner of the Joslin Diabetes Center and a research partner of the Harvard/Dana-Farber Cancer Center. BIDMC is the official hospital of the Boston Red Sox.

Bonnie Prescott | EurekAlert!
Further information:
http://www.bidmc.harvard.edu
http://www.bidmc.org

More articles from Life Sciences:

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

nachricht New gene catalog of ocean microbiome reveals surprises
18.08.2017 | University of Hawaii at Manoa

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New gene catalog of ocean microbiome reveals surprises

18.08.2017 | Life Sciences

Astrophysicists explain the mysterious behavior of cosmic rays

18.08.2017 | Physics and Astronomy

AI implications: Engineer's model lays groundwork for machine-learning device

18.08.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>