The human immune system is a highly complex network of cells, signals, and responses that is tightly regulated to ensure that the body can fight infection without damaging its own tissues. Now, researchers from Japan report a new way the immune system protects lung tissue from viral infections.
In a study published in Cell Reports, researchers from the Nara Institute of Science and Technology (NAIST) have revealed that antigen-specific killer T cells (CD8+ T cells) expand rapidly in the lungs when they encounter alveolar macrophages (AM) that present antigens to protect against viral infection.
CD8+ T cells confer protective immunity against infection by respiratory viruses, such as influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by killing infected cells. To target the correct cells for killing, naïve CD8+ T cells must be primed by contact with antigen-presenting cells (APCs), which mediate the uptake of virus-infected cells and present their antigens, in a process known as cross-presentation. . The primed CD8+ T cells are then clonally expanded and differentiate into long-lived antigen-specific effector or memory T cells.
“Multiple cell types can present antigens to CD8+ T cells in the lungs, although the role of tissue-resident macrophages in this process is unclear,” explains Takumi Kawasaki, lead author of the study. “AMs are the first cells in the lungs to encounter infectious materials, environmental particles, surfactants, and dying cells, and are important in host defense against bacterial and fungal infections, so we suspected they were also important in protecting against respiratory viruses. infection.”
To test this, the researchers explored the mechanisms by which APCs instruct antigen-specific CD8+ T cells in the lungs. Mice were first vaccinated with a specific antigen or infected with IAV, and then subjected to secondary immunization or reinfection.
“We determined that antigen-presenting MAs present inhaled antigen to memory CD8+ T cells,” says study lead author Taro Kawai, “and that this resulted in a rapid expansion of antigen-specific CD8+ T cells in the lungs”.
In addition, the researchers found that MAs help to develop the population of resident memory cells through the production of interleukin 18. Importantly, administration of antigen-laden MAs to mice induced the proliferation of resident memory CD8+ T cells. .
“This strategy may enhance the efficacy of CD8+ T cell-dependent cellular immunity,” says Kawai.
Since the lung is an important tissue for IAV and SARS-CoV-2 infection, it is hoped that the findings from this study on the expansion mechanism of lung-resident memory CD8+ cells will lead to the development of new vaccines that induce cellular immunity. MAs that present virus-specific antigens could be administered as a type of “cell transplant vaccine” in the future.
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Materials provided by Nara Institute of Science and Technology. Note: Content can be edited for style and length.
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