Alveolar macrophages help CD8+ T cells protect against viral infections

The human immune system is a highly complex network of cells, signals, and responses that are tightly regulated to ensure that the body can fight off infection
without damaging its own tissues.
Now, researchers from Japan report a new way
for the immune system to protect lung tissue from viral infections.

Recently, researchers at the Nara Institute of Science and Technology (NAIST) in Japan found that antigen-specific killer T cells (CD8⁺ T cells) expand rapidly in the lungs when they encounter antigen-presenting alveolar macrophages (AMs) to prevent viral infection
.

CD8⁺ T cells provide protective immunity
against infection with 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 right cells for killing, naïve CD8⁺ T cells must be initiated by contact with antigen-presenting cells (APCs), which mediate the uptake of virus-infected cells and present their antigens, a process known as cross-presentation
.
CD8⁺ is then primed and then clonal expansion of T cells and differentiation into effector cells or long-lived antigen-specific memory T cells
.

"Multiple cell types can present antigen⁺ to CD8," explains study lead author Takumi Kawasaki, "the role of T cells in the lung, although the role of tissue macrophages in this process is unclear
.
" "AMs are the first cells in the lungs to encounter infectious substances, environmental particles, surfactants, and dead cells, which are important for host defense against bacterial and fungal infections, so we suspect they are also important
in protecting against respiratory viral infections.
"

To verify this, the researchers explored the mechanism by which APCs direct antigen-specific CD8 ⁺ T cells
in the lung.
First, mice are inoculated or IAV with specific antigens, followed by secondary immunization or reinfection
.

"We determined that antigen-presenting AMs present inhaled antigens to memory CD8⁺, resulting in rapid expansion of antigen-specific CD8 ⁺ T cells
in the lungs.
"

In addition, the researchers found that AMs help develop a population of resident memory-type cells by producing interleukin-18
.
Importantly, mice injected with antigen-loaded AMs induced proliferation of resident memory CD8 ⁺ T cells
.

"This strategy may improve the efficacy of CD8 ⁺ cellular immunity that relies on T cells," Kawai said
.

Given that the lung is the main tissue of IAV and SARS-CoV-2 infection, the discovery of the expansion mechanism of memory CD8+ cells in the lung is expected to lead to the development of
new vaccines to induce cellular immunity.
Virus-specific antigen-presenting AMs could be used as a "cell transplant vaccine"
in the future.