Researchers Identify Immune Cells That Promote Growth of Beta Cells in Type 1 Diabetes

Joslin researchers have identified immune cells that promote growth of beta cells in type 1 diabetes. This study provides further evidence of a changed role for immune cells in type 1 diabetes pathology. [Video]
The study was published online Sept. 27 and will appear in the January issue of Diabetes.
"In type 1 diabetes, the immune system infiltrates pancreatic islets and destroys insulin-producing beta cells. While infiltrating immune cells are traditionally considered to negatively impact beta cells, recent studies in non-obese diabetic (NOD) mice have suggested that immune cells can also contribute to preserving beta cells," says lead author Dr. Ercument Dirice, research fellow in the Kulkarni Lab in the Section on Islet Cell and Regenerative Biology at Joslin Diabetes Center .
This finding is strengthened by the observation by Joslin researchers who reported that members of the Center’s 50-Year Medalist Study, who have lived with type 1 diabetes for 50 years or more, retain some beta cells and produce insulin.
"The traditional view of type 1 diabetes was that immune cells killed all beta cells and people with the disease would have to take insulin for life. But we know that some beta cells do survive and secrete insulin even when the patients have had type 1 diabetes for 50 years," says senior author Dr. Rohit N. Kulkarni, Associate Professor of Medicine at Harvard Medical School and the principle investigator of the project at Joslin. In this study,
Joslin researchers were interested in learning exactly how immune cells could promote beta cell growth and identifying the type of cell and the mechanisms underlying this effect.
In a series of experiments, the researchers injected NOD mice with immune cells from the pancreatic islets of donor NOD mice and assessed their effects on beta cells. The immune cells tested included subtypes of B or T immune cells.
Dirice, the lead author of the study, found that it is T cells not B cells that are associated with beta cell proliferation. Mice that received B cells showed no difference in beta cell growth. Mice that received the T cell subtypes CD4+ and CD8+ showed an elevation in all markers of beta cell proliferation compared to mice that did not receive them. The researchers also found that beta cell growth happens after islets are infiltrated by immune cells and is independent of the effects of glucose and insulin.
Further experiments with cell cultures showed that CD4+ and CD8+ cells secrete inflammatory cytokines and chemokines (Interleukin 2, Interleukin 6, Interleukin 10, MIP-1α and RANTES), which together enhanced beta cell proliferation. This is the first study to report that this group of "soluble factors" is involved in promoting beta cell growth.
"This gives us new insights into what is happening in the pathology of type 1 diabetes. The immune cells we identified send signals which appear to protect and promote growth of beta cells. This opens up an exciting new area that scientists have thought about; now we have the hard data to substantiate it," says Dr. Kulkarni.
The next step is to investigate the effects of immune cells on human beta cell growth. The factors secreted from CD4+ and CD8+ cells are potential therapeutic candidates to enhance beta cell growth to prevent or delay the onset of type 1 diabetes.
"We need to learn more about the relationship of beta cell death and proliferation to determine if we can harness these soluble substances to encourage beta cell proliferation rather than destruction," says Dr. Kulkarni.

Nanoparticle Vaccine May Offer Protection Against Many Infectious Diseases

Many viruses and bacteria infect humans through mucosal surfaces, such as those in the lungs, gastrointestinal tract and reproductive tract. To help fight these pathogens, scientists are working on vaccines that can establish a front line of defence at mucosal surfaces.
Vaccines can be delivered to the lungs via an aerosol spray, but the lungs often clear away the vaccine before it can provoke an immune response. To overcome that, MIT engineers have developed a new type of nanoparticle that protects the vaccine long enough to generate a strong immune response — not only in the lungs, but also in mucosal surfaces far from the vaccination site, such as the gastrointestinal and reproductive tracts.
Such vaccines could help protect against influenza and other respiratory viruses, or prevent sexually transmitted diseases such as HIV, herpes simplex virus and human papilloma virus, says Darrell Irvine, an MIT professor of materials science and engineering and biological engineering and the leader of the research team. He is also exploring use of the particles to deliver cancer vaccines.
“This is a good example of a project where the same technology can be applied in cancer and in infectious disease. It’s a platform technology to deliver a vaccine of interest,” says Irvine, who is a member of MIT’s Koch Institute for Integrative Cancer Research and the Ragon Institute of Massachusetts General Hospital, MIT and Harvard University.
Irvine and colleagues describe the nanoparticle vaccine in the Sept. 25 issue of Science Translational Medicine. Lead authors of the paper are recent PhD recipient Adrienne Li and former MIT postdoc James Moon.

Sturdier vaccines

Only a handful of mucosal vaccines have been approved for human use; the best-known example is the Sabin polio vaccine, which is given orally and absorbed in the digestive tract. There is also a flu vaccine delivered by nasal spray, and mucosal vaccines against cholera, rotavirus and typhoid fever.
To create better ways of delivering such vaccines, Irvine and his colleagues built upon a nanoparticle they developed two years ago. The protein fragments that make up the vaccine are encased in a sphere made of several layers of lipids that are chemically “stapled” to one another, making the particles more durable inside the body.
“It’s like going from a soap bubble to a rubber tire. You have something that’s chemically much more resistant to disassembly,” Irvine says.

Cryoelectron microscope image of the nanoparticles developed by MIT researchers to deliver vaccines to mucosal surfaces. Image: Adrienne Li and Dong Soo Yun

This allows the particles to resist disintegration once they reach the lungs. With this sturdier packaging, the protein vaccine remains in the lungs long enough for immune cells lining the surface of the lungs to grab them and deliver them to T cells. Activating T cells is a critical step for the immune system to form a memory of the vaccine particles so it will be primed to respond again during an infection.

Stopping the spread of infection

In studies of mice, the researchers found that HIV or cancer antigens encapsulated in nanoparticles were taken up by immune cells much more successfully than vaccine delivered to the lungs or under the skin without being trapped in nanoparticles.
HIV does not infect mice, so to test the immune response generated by the vaccines, the researchers infected the mice with a version of the vaccinia virus that was engineered to produce the HIV protein delivered by the vaccine.
Mice vaccinated with nanoparticles were able to quickly contain the virus and prevent it from escaping the lungs. Vaccinia virus usually spreads to the ovaries soon after infection, but the researchers found that the vaccinia virus in the ovaries of mice vaccinated with nanoparticles was undetectable, while substantial viral concentrations were found in mice that received other forms of the vaccine.
Mice that received the nanoparticle vaccine lost a small amount of weight after infection but then fully recovered, whereas the viral challenge was 100 percent lethal to mice who received the non-nanoparticle vaccine.
“Giving the vaccine at the mucosal surface in the nanocapsule form allowed us to completely block that systemic infection,” Irvine says.
The researchers also found a strong memory T cell presence at distant mucosal surfaces, including in the digestive and reproductive tracts. “An important caveat is that although immunity at distant mucus membranes following vaccination at one mucosal surface has been seen in humans as well, it’s still being worked out whether the patterns seen in mice are fully reproduced in humans,” Irvine says. “It might be that it’s a different mucosal surface that gets stimulated from the lungs or from oral delivery in humans.”
Melissa Herbst-Kralovetz, an assistant professor of basic medical sciences at the University of Arizona College of Medicine, says the nanoparticles are “an exciting and effective strategy for inducing effector-memory T-cell responses to nonreplicating subunit vaccines through mucosal vaccination.”
“More research will need to be conducted to determine the delivery approach to be used in humans, but this vaccination strategy is particularly important for diseases that may require significant T cell-mediated protection, such as HIV,” says Herbst-Kralovetz, who was not part of the research team.

Tumour defence

The particles also hold promise for delivering cancer vaccines, which stimulate the body’s own immune system to destroy tumours.
To test this, the researchers first implanted the mice with melanoma tumors that were engineered to express ovalbumin, a protein found in egg whites. Three days later, they vaccinated the mice with ovalbumin. They found that mice given the nanoparticle form of the vaccine completely rejected the tumours, while mice given the uncoated vaccine did not.
Further studies need to be done with more challenging tumour models, Irvine says. In the future, tests with vaccines targeted to proteins expressed by cancer cells would be necessary.
The research was funded by the National Cancer Institute, the Ragon Institute, the Bill and Melinda Gates Foundation, the U.S. Department of Defense and the National Institutes of Health.
The nanoparticle technology has been patented and licensed to a company called Vedantra, which is now developing infectious-disease and cancer vaccines.

10 Most Beautiful Waterfalls in the World

01 Angel Falls, Venezuela

Angel Falls — Venezuela, Photo — Link

The first on our list is a waterfall Angel – the highest in the world. His height – 979 meters, which is 15 times greater than the height of the famous Niagara Falls. The waterfall is in Venezuela, in Canaima National Park, and every year thousands of tourists come into the country specifically to see this wonder of nature with his own eyes, and BASE jumpers are risky even jump with it. The waterfall is named after American aviator Jimmie Angel, who, while flying over Venezuela, observed from a height of this waterfall and discovered it around the world.

02 Iguazu Falls, Brazil

Iguazu Falls — Brazil, Photo — Link

This waterfall, located on the border of Brazil and Argentina, is considered one of the most powerful in the world. In fact, Iguazu – it’s not a waterfall, but a whole system of 275 waterfalls in height from 60 to 80 meters and a length of about 3 kilometers. The largest waterfall – it’s a natural formation in the shape of U, called the Spanish conquistadors’ throat the devil. ”

03 Waterfalls Plitvice Lakes, Croatia

Waterfalls Plitvice Lakes — Croatia, Photo — Link

These amazingly beautiful waterfalls are located in Croatia, Plitvice Lakes National Park. Lake of the national park are varied colors, from bright blue to dark blue, depending on the types of microorganisms that are found in them. Several waterfalls, connecting the lake, look at the background of green and blue waters of the surrounding forest was amazing.

04 Niagara Falls, USA

Niagara Falls — USA, Photo — Link

Of course, it was impossible to ignore one of the most famous waterfalls in the world – Niagara Falls in the north-eastern United States. He is also one of the most powerful in the world – about 2.8 million liters of water per second, just think! Tourists like to Niagara Falls because it is relatively easy to access and view from all sides.

05 Victoria Falls, Zimbabwe

Victoria Falls —Zimbabwe, Photo — Link

Another famous and very beautiful waterfall in Zimbabwe – is, of course, the Victoria Falls. His height – 108 meters, power – one million liters per second, and fans are really thrills can take a long jump from the waterfall on the rubber stretch.

06 Falls of Yosemite, USA

Falls of Yosemite — USA, Photo — Link

This waterfall can be seen in California in the same national park. Yosemite – one of the highest waterfalls in the world – 739 meters. Interestingly, the waterfall in winter almost “calms down” and in the spring and summer reaches its maximum amplitude.

07 Kaieteur Falls, Guyana

Kaieteur Falls — Guyana, Photo — Link

This marvel of nature hidden in the tropical forests of Guyana, a country in South America. Kaieteur – one of the largest waterfalls in the world. His height – about 226 meters. For a long time about this waterfall, known only to locals, but in 1870 he accidentally discovered by English geologist. To get to the waterfall is quite difficult, but it does not stop the flow of tourists wanting to see Kaieteur own eyes.

08 Gallfoss Falls, Iceland

Gallfoss Falls — Iceland, Photo — Link

Not all of the beautiful waterfalls located in the tropics – there are those that are located far to the north, for example, an amazing waterfall Gallfoss Icelandic in Iceland, a country that is famous for its natural wonders. Gallfoss – one of the most powerful waterfall in Europe, although his height – only about 30 meters.

09 Waterfall Dettifoss, Iceland

Waterfall Dettifoss — Iceland, Photo — Link

Another Icelandic waterfall – Dettifoss, the most powerful in Europe. His height – 40 meters, and power – about 200 cubic meters of water per second. The waterfall is surrounded by beautiful cliffs, gorges and lakes and is very popular both among locals and tourists.

10 Sutherland Falls, New Zealand

Sutherland Falls — New Zealand, Photo — Link

In New Zealand there is a waterfall called Sutherland. It is located on the South Island and is considered one of the most beautiful and mysterious waterfalls in the world. To get to the waterfall is not easy, but it’s worth – a narrow water jet, flying at an elevation of 580 meters, surrounded by thick foliage and rocks is a fantastic sight!