Lung Organoid That Keeps Immune Cells Alive Controls Virus With Resident T Cells
Researchers grew pieces of human lung tissue intact to make organoids that contain T, B and NK cells, and confirmed the defensive function of tissue-resident memory T cells.
Conventional organoids usually grow only epithelial cells, which made it hard to see immune responses together in infection experiments. Researchers at Stanford University in the United States reported in Nature a human lung organoid that keeps the immune cells within lung tissue alive.
Culturing tissue pieces whole to preserve immune cells
The researchers grew pieces of adult distal lung tissue for a long period in a three-dimensional air-liquid interface culture without dissociating them. As a result, the epithelium and supporting tissue (stroma), along with the T cells, B cells, natural killer cells and myeloid cells in the tissue, were maintained together. T cells in the organoid expressed tissue-resident and memory markers and preserved the same T cell receptor (TCR) repertoire as the original tissue.
When the organoids were infected with SARS-CoV-2, the virus multiplied in the epithelium and inflammatory cytokines were secreted, and virus-specific tissue-resident memory T cell (TRM) responses were induced. Conversely, when T cells in the organoid were stimulated in advance with viral peptides, later infection was suppressed. The result shows that memory T cells in the lung itself contribute to defense even without secondary lymphoid tissue.
Limits
This is an in vitro model derived from human tissue and does not reproduce blood vessels, nerves or the entry of systemic immunity. Differences between donor tissues are large, and the effect of local vaccination strategies must be verified separately in people.
- A human lung organoid grown from whole tissue pieces in 3D culture that preserves T, B, NK and myeloid cells
- Organoid T cells kept resident and memory markers and the TCR repertoire of the original tissue
- Virus-specific TRM responses were induced by SARS-CoV-2 infection, and prior peptide stimulation suppressed infection
Limitations An in vitro model based on human tissue that lacks blood vessels and entry of systemic immunity, with large variation between donors; local vaccination strategies need separate verification in people.
Original Research
- Rathkey JK, Choi SS, van Unen V, … Kuo CJ · Stanford University School of Medicine (USA). Human lung organoid modelling of tissue-resident antiviral T cell responses. Nature. DOI: 10.1038/s41586-026-11114-1
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