When it comes to the flu, the nose has a long memory

After an influenza infection, the nose recruits immune cells with long memories to keep watch for the virus, research with mice suggests.

For the first time, this type of immune cell — known as tissue resident memory T cells — has been found in the nose, researchers report June 2 in Science Immunology. Such nasal resident memory T cells may prevent flu from recurring. Future nasal spray vaccines that boost the number of these T cells in the nose might be an improvement over current flu shots, researchers say.

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It’s known that some T cell sentinels take up residence in specific tissues, including the brain, liver, intestines, skin and lungs. In most of these tissues, the resident memory T cells start patrolling after a localized infection. “They’re basically sitting there waiting in case you get infected with that pathogen again,” says Linda Wakim, an immunologist at the University of Melbourne in Australia. If a previous virus invades again, the T cells can quickly kill infected cells and make chemical signals, called cytokines, to call in other immune cells for reinforcement. These T cells can persist for years in most tissues.

It’s different in the lungs. There, resident memory T cells have shorter-term memories than ones that reside in other tissues, scientists have previously found. To see if all tissues in the respiratory tract have similarly forgetful immune cells, Wakim and colleagues tagged immune cells in mice and sprayed flu virus in the rodents’ noses. After infection, resident memory T cells settled into the nasal tissue. The researchers haven’t yet dissected any human noses, but it’s a pretty good bet they also contain resident memory T cells, Wakim says.

Unlike in the lungs, the nose T cells had long memories, persisting for a least a year. “For mice, that’s quite a long time, almost a third of their life,” Wakim says. She doesn’t yet know why there’s a difference between nose and lung T cell memories, but finding out may enable researchers to boost lung T cell memory.

Still, with nose T cells providing security, the lungs might not need much flu-fighting memory. Memory T cells that patrol only the upper respiratory tract could stop viruses from ever reaching the lungs, Wakim’s team found. An injection of virus under the skin didn’t produce any resident memory T cells in the respiratory tract. Those findings could mean that vaccines delivered via nasal spray instead of shots might stimulate memory T cell growth in the nose and could protect lungs from damage as well. A nasal spray called FluMist has had variable results in people. No one knows if that vaccine can produce nasal memory T cells.

It’s not surprising to find that the nose has its own resident memory T cell security force, says Troy Randall, a pulmonary immunologist at the University of Alabama at Birmingham. “But it’s a good thing to know and certainly they’re the first to show it.”

The discovery may direct some research away from the lungs and toward the nose, Randall says. Future research should focus on how the resident memory T cells work with memory B cells that produce antibodies against viruses and bacteria, he suggests.