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 New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>