T cell exhaustion and immune-mediated disease — the potential for therapeutic exhaustion. (December 2016)

• Record Type: Journal Article
• Authors: McKinney, Eoin F; Smith, Kenneth GC
• Is Part Of: Current opinion in immunology. Volume 43(2016)
• Page Start: 74
• Page End: 80
• Publication Date: 2016-12
• Subjects: Immunology -- Periodicals; Allergy -- Periodicals; Immunology -- Abstracts -- Periodicals; Allergy -- Abstracts -- Periodicals; 616.079
• DOI: 10.1016/j.coi.2016.09.005
• Languages: English
• ISSNs: 0952-7915

Abstract

Highlights: T cell exhaustion represents a continuous spectrum of CD8 T cell dysfunction defined in models of chronic viral infection. It is associated with persistent viraemia and is a target of immune checkpoint therapy in cancer. By contrast it is associated with favourable long-term outcome in chronic inflammatory diseases. Modulation of inhibitory receptor signalling can reverse exhaustion in chronic infection and cancer and may prove a useful strategy to modulate the long-term course of immune-mediated disease. Understanding the biology underlying immune responses to chronic infection may inform the biology determining clinical outcome in autoimmunity. Abstract : T cell exhaustion represents a continuous spectrum of cellular dysfunction induced during chronic viral infection, facilitating viral persistence and associating with poor clinical outcome. Modulation of T cell exhaustion can restore function in exhausted CD8 T cells, promoting viral clearance. Exhaustion has also been implicated as playing an important role in anti-tumour responses, whereby exhausted tumour-infiltrating lymphocytes fail to control tumour progression. More recently exhaustion has been linked to long-term clinical outcome in multiple autoimmune diseases but, in contrast to cancer or infection, it is associated with a favourable clinical outcome characterised by fewer relapses. An increasing understanding of key inhibitory signals promoting exhaustion has led to advances in therapy for chronic infection and cancer. An increasing understanding of this biology may facilitate novel treatment approaches for autoimmunity through the therapeutic induction of exhaustion.