The way in which immune system exhaustion occurs and what steps can be taken to revitalize anti-viral immune responses is reported online in Nature Immunology.
Viral infections, such as the common cold or influenza, trigger the immune system. Specific ‘killer’ cells known as CD8+ T cells attack virally infected cells, thereby destroying the offending viruses and the patients usually recover within a matter of days. However, some persistent infections, such as hepatitis viruses and HIV, create infections that the immune system fails to cure.
John Wherry and colleagues explored the basis for this immune non-response. They find chronic infection in mice disarms their killer cells by causing them to express multiple ‘inhibitory receptors’. Expression of these receptors is not random, but occurs in a specific order such that more severe infections prompt the expression of a more diverse array of inhibitory receptors. By blocking multiple ‘inhibitory’ receptors, the team could restore the ‘killing’ activity of the CD8+ T cells.
The authors plan on future studies to determine whether inhibitory receptor blockade might ‘rejuvenate’ exhausted T cells during chronic infections in humans.