The human immune system is a very complex network of cells, signals and responses that is tightly regulated to ensure that the body can fight infections without damaging its own tissues. Now, Japanese researchers are reporting a new way the immune system protects lung tissue from viral infections.
In a study published in Cell reportsresearchers from the Nara Institute of Science and Technology (NAIST) have revealed that antigen-specific killer T cells (CD8+ T cells) grow rapidly in the lungs when they encounter antigen-presenting alveolar macrophages (AMs) 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. In order to target the right cells to kill, naive 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. Primed CD8+ The T cells then grow by cloning and differentiate into long-lived antigen-specific effector or memory T cells.
“Several types of cells can present the antigen to CD8+ T cells in the lungs, although the role of tissue-resident macrophages in this process is unclear,” says Takumi Kawasaki, lead author of the study. “AMs are the first cells in the lung that encounter infectious material, environmental particles, surfactants, and dying cells, and they are important for host defense against bacterial and fungal infections, so we suspected that they were also important in the protection against viral respiratory infections.
To test this, the researchers explored the mechanisms by which APCs instruct antigen-specific CD8+ T cells in the lungs. First, the mice were primed by vaccination with a specific antigen or infection with IAV, then they were subjected to secondary immunization or reinfection.
“We determined that antigen-presenting AMs present inhaled antigen to CD8 memory+ T-lymphocytes,” says lead study author Taro Kawai, “and that this resulted in a rapid expansion of antigen-specific CD8+ T cells in the lungs.”
Additionally, the researchers found that AMs help develop a population of resident memory-like cells by producing interleukin 18. Importantly, administration of antigen-loaded AMs to mice induced the proliferation of resident memory type CD8.+ T cells.
“This strategy can improve the efficiency of CD8+ T cell-dependent cellular immunity,” says Kawai.
Since the lung is a major tissue for IAV and SARS-CoV-2 infection, the results of this study regarding the mechanism of expansion of lung-resident CD8+ memory cells should lead to the development of new vaccines that induce cellular immunity. AMs with virus-specific antigens could be given in the future as a type of ‘cell transplant vaccine’.
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Material provided by Nara Institute of Science and Technology. Note: Content may be edited for style and length.