- Influenza A virus (IAV) is a seasonal pathogen with the potential to cause devastating pandemics.
- Type A influenza infection can be serious and cause widespread outbreaks and disease.
- IAV infects multiple epithelial cell subsets in the respiratory tract, eliciting damage to the lungs.
- Epithelial cells line the outer surfaces of organs and blood vessels throughout the body, as well as the inner surfaces of cavities in many internal organs.
- Clearance of IAV is primarily dependent on CD8+ T cells, which must balance control of the infection with immunopathology.
- CD8+ T-cell is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways.
- Immunopathology a branch of medicine that deals with immune responses associated with disease.
- Using a virus expressing Cre recombinase to permanently label infected cells in a Cre-inducible reporter mouse, we previously discovered infected club cells that survive both lytic virus replication and CD8+ T cell-mediated clearance.
- Cre recombinase is a tyrosine recombinase isolated from the bacteriophage P1 that catalyzes the cleavage and ligation of DNA at specific nucleotide recognition sites, loxP sites, via phosphoryl transfer.
- In this study, we demonstrate that ciliated epithelial cells, type I and type II alveolar cells can also become survivor cells.
- Type I alveolar cells are squamous extremely thin cells involved in the process of gas exchange between the alveoli and blood.
- Type II alveolar cells are involved in the secretion of surfactant proteins.
- Survivor cells are stable in the lung long-term and demonstrate enhanced proliferation compared to uninfected cells.
- When we investigated how survivor cells evade CD8+ T cell killing, we observed that survivor cells upregulated the inhibitory ligand PD-L1, but survivor cells did not use PD-L1 to evade CD8+ T cell killing.
- Our data suggest that survivor cells are not inherently resistant to CD8+ T cell killing, but instead no longer present IAV antigen and cannot be detected by CD8+ T cells.
- Finally, we evaluate the failure of CD8+ T cells to kill these previously infected cells.
This work demonstrates that additional cell types can survive IAV infection and that these cells robustly proliferate and are stable long term. By sparing previously infected cells, the adaptive immune system may be minimizing pathology associated with IAV infection.
Al-Shura, Anika Niambi (2020). “Lymphocytes”. Advanced Hematology in Integrated Cardiovascular Chinese Medicine. Elsevier. pp. 41–46. doi:10.1016/b978-0-12-817572-9.00007-0. ISBN 978-0-12-817572-9.
Helper T cells/CD4+ •express CD4 glycoproteins on their cell surface, which activate in the presence of peptide antigens on the surface of invading pathogens; •respond immediately to protect the immune system; •secrete different cytokine proteins according to the immune response.“