An 'exhausted' army of immune cells may not be able to fight off infection, but if its soldiers fight too hard they risk damaging the very body they are meant to be protecting, suggests new research.
In research published today in the journal Nature, scientists from the Cambridge Institute for Medical Research looked at patterns of genes that were turned on and off in patients with autoimmune diseases and found similarities with those seen in people with chronic infection, such as hepatitis C, and cancer: in other words, they have shown that the same process of T cell 'exhaustion' known to be involved in the immune response to chronic infection and cancer is also important in many autoimmune diseases.
full paper http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14468.html
During chronic infection the process of T-cell exhaustion inhibits the immune response, facilitating viral persistence1. Here we show that a transcriptional signature reflecting CD8 T-cell exhaustion is associated with poor clearance of chronic viral infection, but conversely predicts better prognosis in multiple autoimmune diseases. The development of CD8 T-cell exhaustion during chronic infection is driven both by persistence of antigen and by a lack of accessory ‘help’ signals. In autoimmunity, we find that where evidence of CD4 T-cell co-stimulation is pronounced, that of CD8 T-cell exhaustion is reduced.
... Using expression of optimal surrogate markers of co-stimulation/exhaustion signatures in independent data sets, we confirm an association with good clinical outcome or response to therapy in infection (hepatitis C virus) and vaccination (yellow fever, malaria, influenza), but poor outcome in autoimmune and inflammatory disease (type 1 diabetes, anti-neutrophil cytoplasmic antibody-associated vasculitis, systemic lupus erythematosus, idiopathic pulmonary fibrosis and dengue haemorrhagic fever). Thus, T-cell exhaustion plays a central role in determining outcome in autoimmune disease and targeted manipulation of this process could lead to new therapeutic opportunities...