Abstract
During persistent infections, the immune cells responsible for killing infected cells and maintaining inflammation gradually stop functioning, allowing the pathogen to thrive. But can this process be reversed? It's common in chronic viral disease for the immune system to grow accustomed to the infection. Normally CD8 T cells retain a ‘memory’ of the viruses they encounter, so they can respond rapidly to a new infection. In a chronic infection the memory cells lose this capacity, but the nature of this ‘exhausted’ state is not well understood. Barber et al. have now found a possible cause in a study of a mouse infection model. The inhibitory immune receptor gene PD-1 is much more active in exhausted than in normal CD8 T cells, and administration of antibodies that block PD-1 action restores function in virus-specific T cells and also reduces virus levels. The discovery of a T-cell exhaustion mechanism suggests a route to immunological strategies for treating chronic viral infections.
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