07 June 2017

Stimulation of immune cells in the nose will protect against the flu

Daria Spasskaya, N+1

Researchers from The University of Melbourne found that in response to an infection with the influenza virus, tissue-specific immune memory cells appear in the upper respiratory tract, which remain there for a long time and protect the body from repeated infections. Information on how to stimulate the formation of these cells without infection will help to create an effective flu vaccine that will need to be instilled into the nose. The work of Pizzolla et al. Resident memory CD8+ T cells in the upper respiratory tract prevent pulmonary influenza virus infection is published in the journal Science Immunology.

After an illness caused by viruses or bacteria entering the body, the memory of them is stored by special memory T-cells that provide an effective immune response in case of repeated infection. Memory cells can circulate throughout the body along with blood, or sit in one place, in a certain tissue, then they are called resident. Resident cells can provide more effective protection than circulating cells if the antigen is predominantly in contact with a specific tissue.

The influenza virus normally affects the upper respiratory tract, but in some cases it penetrates into the lungs, causing severe complications in the form of viral pneumonia. Also, some varieties of the virus that cause pandemics tend to the lung tissue. Therefore, the attention of immunologists has so far been focused on specific lung protection. It was known that after infection, a population of resident CD8+ T memory cells providing secondary immunity is formed in the lungs, which, however, exists for quite a short time. The immunity of the upper respiratory tract, that is, the nasopharynx, which is in contact with the virus in the first place, remained unexplored.

In their work, a group of Australian immunologists showed that the nasopharynx has its own immunity against the flu virus. Infecting mice with the virus intranasally (through the nose), scientists found that in response to infection, a population of specific resident CD8+ T memory cells is formed in the epithelial tissue of the upper respiratory tract, which remain there for at least four months after infection. Repeated infection after 120 days showed that the population of resident cells had not decreased during this time and was still able to effectively fight the virus. In addition, nasopharyngeal-specific T cells prevented the virus from spreading to the lungs. 

Figure from an article in Science Immunology: T cells in the nasal epithelium of a mouse after infection.
Virus-specific T cells are marked with a red fluorescent marker.

The scientists also tried to understand what factors are important for the formation of specific nasopharyngeal T cells in order to artificially stimulate this process. It turned out that the standard set of molecular signals necessary for the formation of resident cells, such as the growth factor TGFß, has little effect on the nasopharyngeal population. However, the authors of the work managed to select a set of epitope molecules that, as part of the virus, contributed to the colonization of the mouse nasopharynx with specific T cells, which is already a step towards the development of a vaccine.

Currently, there are intranasal forms of influenza vaccine on the market that contain a live attenuated virus. Their introduction stimulates the formation of antibodies against influenza antigens in the lymphoid tissue adjacent to the mucous membrane. The effectiveness of such vaccines is limited. The authors propose a completely different principle of the vaccine, based on the stimulation of T-cell immunity. If the invention works in humans, it is possible that flu vaccines will become more effective and will depend less on the seasonal representation of virus varieties.

Portal "Eternal youth" http://vechnayamolodost.ru  07.06.2017

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