Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Reservoir divers: Select antiviral cells can access HIV's hideouts

01.02.2017

Persistent infected cells live in germinal centers

When someone is HIV-positive and takes antiretroviral drugs, the virus persists in a reservoir of infected cells. Those cells hide out in germinal centers, specialized areas of lymph nodes, which most "killer" antiviral T cells don't have access to.


The green areas are B cell follicles within germinal centers, specialized areas of lymph nodes where HIV-infected cells hide out. Red spots indicate antiviral T cells.

Credit: Rama Rao Amara, Emory Vaccine Center

Scientists at Yerkes National Primate Research Center, Emory University, have identified a group of antiviral T cells that do have the entry code into germinal centers, a molecule called CXCR5.

Knowing how to induce antiviral T cells displaying CXCR5 will be important for designing better therapeutic vaccines, as well as efforts to suppress HIV long-term, says Rama Rao Amara, PhD, professor of microbiology and immunology at Yerkes National Primate Research Center and Emory Vaccine Center.

... more about:
»HIV »T cells »Vaccine »lymph nodes

The findings are scheduled for publication in PNAS the week of Jan. 30, 2017.

"We think these cells are good at putting pressure on the virus," Amara says. "They have access to the right locations - germinal centers - and they're functionally superior."

Amara and his colleagues looked for these antiviral cells in experiments with rhesus macaques, which were vaccinated against HIV's relative SIV and then repeatedly exposed to SIV. The vaccine regimens were described in a previous publication.

The vaccines provided good but imperfect protection against pathogenic SIV, which means that a group of 20 animals ended up infected, with a range of viral levels. In some animals, a large fraction (up to 40 percent) of anti-viral CD8 T cells in lymph nodes displayed CXCR5. Having more CXCR5-positive antiviral T cells was strongly associated with better viral control, the researchers found.

T cells can be divided into "helper" cells and "killer" cells, based on their function and the molecules they have on their surfaces. A group of T cells called follicular helper T cells or Tfh cells were already known to be in germinal centers and to display CXCR5. Tfh cells are also considered a major reservoir for HIV and SIV.

When stimulated outside the body, the CXCR5-positive cells can attack and kill virus-infected Tfh cells. Some of the killer cells lose CXCR5 upon stimulation, but adding an immune regulatory molecule called TGF-beta can boost the CXCR5 levels.

Co-corresponding author Vijayakumar Velu, PhD, assistant professor at Yerkes, says the CXCR5+ killer cells the team has identified have stem cell-like properties, because they have the capacity to differentiate into both CXCR5+ and CXCR5- cells. The lab of co-author Rafi Ahmed, director of Emory Vaccine Center, has reported analogous cells in mice with chronic viral infections. In addition, a recent Science Translational Medicine paper found similar cells in HIV-infected humans, calling them "follicular CD8 T cells."

"These cells have the potential to infiltrate sites of ongoing viral replication and persistence," Amara says. "Their properties and the ability to induce these cells by vaccination provide a tremendous opportunity to target and reduce the viral reservoir in lymphoid tissues."

###

The first author of the paper is former Immunology and Molecular Pathogenesis graduate student Geetha Mylvaganam, PhD, now at Massachusetts General Hospital. Emory and Yerkes co-authors include Daniel Rios, PhD, Gregory Tharp, Maud Mavinger, PhD, Sakeenah Hicks, Smita Iyer, PhD, Rafi Ahmed, PhD, Ifor Williams, MD, PhD, Ann Chahroudi, MD, PhD and Steven Bosinger PhD.

Amara is a co-inventor of vaccine technology described in the paper, and Emory has licensed the technology to Geovax.

The research was supported by the National Institute of Allergy and Infectious Diseases (R36AI112787, P01AI88575 and U19 AI109633), the Office of Research Infrastructure Programs (Primate centers: P51OD11132) and the Emory Center for AIDS Research (P30AI050409).

Quinn Eastman | EurekAlert!

Further reports about: HIV T cells Vaccine lymph nodes

More articles from Health and Medicine:

nachricht GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>