Scientists discover unique immune cell populations ready to combat SARS-CoV-2 in the upper airway.
Researchers from the La Jolla Institute for Immunology (LJI) have conducted the first detailed study of immune cell memory in the upper airways of adult participants. They identified “tissue resident” memory cells among these immune cells, which are positioned to protect the airway from SARS-CoV-2 and various respiratory infections.
“We were finally able to investigate the details of how infections occur — what takes place when a virus invades the tissues in the upper airway,” explains Sydney Ramirez, M.D., Ph.D., an instructor at LJI and lead author of the study published in Nature.
The research team gained insights into how immune cells that inhabit the nasal passages collaborate with those that flow through the bloodstream. Together, these immune cell types are crucial in combating upper airway infections and establishing long-term immunity against certain pathogens.
“Our findings reveal that a significant amount of immune memory exists within your upper airway. This implies that you don’t necessarily have to wait for immune cells from other parts of the body to arrive to address an infection,” states Shane Crotty, Ph.D., a professor at LJI and senior author of the study.
The researchers believe these insights may contribute to the development of improved vaccines aimed at enhancing immune defense. “This discovery aids our understanding of immunity to pathogens and may lead to new vaccines against airway-infecting viruses,” Crotty added.
Immune cells in the airway
The study found that immune cells like T cells and B cells respond actively to vaccination or infection with SARS-CoV-2. They recorded a wide range of T cells and B cells, each serving different roles in immunity and inflammation.
Moreover, the researchers identified that the airway contains populations of virus-specific memory immune cells, including tissue-resident memory T cells, memory B cells, and antibody-producing cells. Memory B cells can produce strong antiviral and antibacterial antibodies that defend the nose and throat against infections.
Ramirez describes the identification of these long-lasting immune cells as “truly remarkable.” These specialized “tissue resident” immune cells are designed to live in the upper airway and can persist for at least six months.
Role of adenoids
The study also revealed that adenoids become more active in response to infections. Adenoids are specialized immune tissues located at the back of the nasal passages, right above the throat. They monitor the air we inhale and contain germinal centers, which generate B cells that produce antibodies against diseases.
Adenoids are known to reduce in size during adulthood. “Many medical researchers believed that once you reach a certain age, your tonsils and adenoids would disappear,” Ramirez noted.
However, the current research indicates that even older participants still possess pathogen-fighting cells within their adenoid tissue. These B cells in the “germinal centers” are specifically trained to combat viruses like SARS-CoV-2. The scientists also discovered T follicular helper cells, which play a crucial role in signaling B cells within the germinal centers.
“These cells are extremely important, and obtaining samples of them has been challenging in the past,” commented Paul Lopez, Ph.D., a co-author and Research Technician in the Crotty Lab who collaborated closely with Farhoud Faraji, M.D., Ph.D., and L. Benjamin Hills, M.D., Ph.D., from UC San Diego.
Advanced collection methods
Many diseases gain a foothold in the body by initially infecting the upper airway. Previously, it was quite difficult to collect samples from these cells, and those collected often proved to be too damaged for analysis.
In this study, the researchers collaborated with LJI Clinical Director Gina Levi, R.N., and clinical coordinators at LJI’s John and Susan Major Center for Clinical Investigation to create a new swabbing method to gather these hard-to-reach immune cells.
Levi’s team met with participants monthly, using swabs to obtain immune cells from their nasal passages. To ensure the swabs targeted the correct tissues and effectively sampled the adenoids, the LJI team collaborated with UC San Diego’s surgical specialists, Carol H. Yan, MD, and Adam S. DeConde, MD, who utilized endoscopy techniques to document the sample collection site within the nasal cavity.
Timeliness was critical for successful sampling. The researchers discovered they could prevent cell loss and degradation by processing samples on the same day rather than freezing the cells.
“My coordinators and I managed to have study subjects swabbed before 1 p.m. daily,” Levi said. “We ensured everything was prepped for immediate processing, and then Sydney would stay late to analyze the samples.”
Future directions in immune measurement
Looking ahead, the LJI researchers are eager to examine how immune cell populations in the airway change in response to intranasal vaccines, like the FluMist influenza vaccine, which is administered through the nose. They are also continuing to monitor some participants to observe how long their populations of beneficial memory B and T cells remain stable.
Lopez suggests that the swabbing technique and analytical methods may also be useful for immunologists studying other immune system components, such as cells associated with chronic rhinosinusitis due to allergies.
“It would be fascinating to evaluate immune cells during various disease states and perhaps utilize this information as a potential diagnostic tool in the future,” Lopez remarked.
Other contributors to the study ‘Immunological memory diversity in the human upper airway’ included Benjamin Goodwin, Hannah D. Stacey, Henry J. Sutton, Kathryn M. Hastie, Erica Ollmann Saphire, Hyun Jik Kim, and Sara Mashoof.
This research received support from the National Institutes of Health (NIH, T32 AI007036), the NIH National Institute of Allergy and Infectious Diseases (NIAID, AI142742), and an A.P. Giannini Foundation fellowship award.
