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CD8 (red) lymphocytes of HIV-control patients in contact with CD4 (green) cells infected with HIV. The nuclei of the cells are in blue. In pink, a cytotoxic molecule secreted by CD8 cells to destroy CD4 cells. Credit: Anastbadia Mikhailova / Pasteur Institute.
The cells of the few individuals who naturally control HIV infection have been researched for nearly 15 years to elucidate their specific characteristics. After researching the ANRS CO21 CODEX and CO6 PRIMO cohorts, scientists from the Institut Pasteur described the characteristics of CD8 immune cells in these "HIV-controlling" subjects. The unique antiviral potency of these immune cells can be attributed to an optimal metabolic program that confers the persistence and ability to react effectively against infected cells. By working ex vivo, scientists managed to reprogram the cells of infected uncontrolled individuals to give them the same antiviral power as the controller cells. Their results are published in the journal Nature Metabolism on July 12, 2019.
Some people have the ability to control HIV naturally without treatment. In these very rare people (less than 1% of people living with HIV), no multiplication of the virus in the blood can be detected after more than 10 years of infection without treatment. In 2007, scientists from the Institut Pasteur described the extraordinary antiviral activity of CD8 lymphocytes in these patients. Unlike noncontrollers, CD8 cells from HIV monitors are able to rapidly destroy infected CD4 cells.
Scientists from the HIV, inflammation and persistence unit of the Pasteur Institute continued their research with the goal of identifying the specific characteristics of these cells so that they could confer the same characteristics to cells of non-controlling subjects.
The CD8 cells (or "memory cells") of the controllers seem identical to those of the non-controllers. But scientists have shown that they have a different molecular program. Their research shows that the anti-HIV CD8 cells of the controllers not only have enormous antiviral potential; they are also programmed to survive, while in non-controllers, the cellular program predisposes them to depletion and cell death.
The CD8 cells of the controllers use various metabolic resources, taking advantage in particular of the energy provided by their mitochondria,[1] which allows the cells to survive in stressful conditions. Conversely, the cells of non – controllers depend on a single source of energy (glucose) and have limited mitochondrial activity. "We have identified that the antiviral activity of CD8 cells in the controllers is badociated with an optimal program that gives them a plasticity in the use of the cell's energy resources," says Asier Saez-Cirion, a scientist at HIV unity, inflammation and persistence of the Institut Pasteur and coordinator. of the study.
In the laboratory, scientists then succeeded in stimulating mitochondrial activity in anti-HIV cells from non-controllers. They used an immune system secreted substance called interleukin 15 (IL-15) to stimulate the mitochondrial activity of non-controller cells and increase their anti-HIV potency. The reprogrammed CD8 cells of the non-controllers are able to destroy the infected CD4 cells, much like the cells of the controllers.
"Our research shows that even though anti-HIV CD8 cells of non-controllers are relatively inefficient compared to those of the controllers, the differences can be overcome," concludes Asier Saez-Cirion.
Metabolic reprogramming of immune cells is a strategy already tested in clinical trials for the treatment of cancer. Scientists hope to be able to test the anti-HIV capabilities of the in vivo strategy in the near future.
Reference
The metabolic plasticity of HIV-specific CD8 + T cells is badociated with increased antiviral potential and natural control of HIV-1 infection.
Mathieu Angin, Stevenn Volant, Caroline Pbadaes, Camille Lecuroux, Valerie Monceaux, Marie-Agnès Dillies, José Carlos Valle-Casuso, Gianfranco Pancino, Gianfranco Pancino, Bruno Vaslin, Roger Le Grand, Laurence Weiss, Cécile Goujard, Laurence Meyer, Faroudy Boufbada , Michaela Müller -Trutwin, Olivier Lambotte & Asier Sáez-Cirión. Nature Metabolism, Volume 1, pages 704-716 (2019), https://doi.org/10.1038/s42255-019-0081-4.
This article has been republished from the following materials. Note: Content may have changed for length and content. For more information, please contact the cited source.
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