The clinical course of autoimmune and @entity166 varies greatly, even between individuals with the same condition. An understanding of the molecular basis for this heterogeneity could lead to significant improvements in both monitoring and treatment. During @entity281 the process of T-cell exhaustion inhibits the immune response, facilitating viral persistence. Here we show that a transcriptional signature reflecting @entity405 T-cell exhaustion is associated with poor clearance of chronic @entity1800 , but conversely predicts better prognosis in multiple @entity792 . The development of @entity405 T-cell exhaustion during @entity281 is driven both by persistence of antigen and by a lack of accessory 'help' signals. In @entity792 , we find that where evidence of @entity404 T-cell co-stimulation is pronounced, that of @entity405 T-cell exhaustion is reduced. We can reproduce the exhaustion signature by modifying the balance of persistent stimulation of T-cell antigen receptors and specific @entity3138 -induced co-stimulation provided to @entity1 @entity405 T cells in vitro, suggesting that each process plays a role in dictating outcome in @entity792 . The 'non-exhausted' T-cell state driven by @entity3138 -induced co-stimulation is reduced by signals through the exhaustion-associated inhibitory receptor @entity8395 , suggesting that induction of exhaustion may be a therapeutic strategy in autoimmune and @entity32 . 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 @entity281 ( @entity20800 ) and vaccination ( @entity22073 , @entity311 , @entity683 ), but poor outcome in autoimmune and @entity32 (type 1 @entity6 , anti-neutrophil cytoplasmic antibody-associated @entity1333 , @entity1252 , @entity2416 and @entity7643 ). Thus, T-cell exhaustion plays a central role in determining outcome in @entity792 and targeted manipulation of this process could lead to new therapeutic opportunities.

T-cell exhaustion, co-stimulation and clinical outcome in XXXX and @entity281 .

@entity1 :: ('9606', 'Species') :: ['human'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammatory disease'] @entity20800 :: ('11103', 'Species') :: ['hepatitis C virus'] @entity404 :: ('920', 'Gene') :: ['CD4'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity1333 :: ('MESH:D014657', 'Disease') :: ['vasculitis'] @entity7643 :: ('MESH:D019595', 'Disease') :: ['dengue haemorrhagic fever'] @entity311 :: ('MESH:D008288', 'Disease') :: ['malaria'] @entity1252 :: ('MESH:D008180', 'Disease') :: ['systemic lupus erythematosus'] @entity405 :: ('925', 'Gene') :: ['CD8'] @entity3138 :: ('914', 'Gene') :: ['CD2'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection', 'chronic infection'] @entity1800 :: ('MESH:D014777', 'Disease') :: ['viral infection'] @entity683 :: ('MESH:D007251', 'Disease') :: ['influenza'] @entity792 :: ('MESH:D001327', 'Disease') :: ['autoimmune disease', 'autoimmunity', 'autoimmune diseases'] @entity2416 :: ('MESH:D054990', 'Disease') :: ['idiopathic pulmonary fibrosis'] @entity8395 :: ('5133', 'Gene') :: ['PD-1'] @entity22073 :: ('MESH:D015004', 'Disease') :: ['yellow fever'] @entity166 :: ('MESH:D003141', 'Disease') :: ['infectious disease']
@entity792 :: (MESH:D001327,Disease) :: ['autoimmunity']
