T cell exhaustion and immune-mediated disease-the potential for therapeutic exhaustion

Curr Opin Immunol. 2016 Dec;43:74-80. doi: 10.1016/j.coi.2016.09.005. Epub 2016 Oct 13.


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.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cellular Senescence
  • Clonal Anergy
  • Humans
  • Immunotherapy / methods*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Neoplasms / immunology*
  • Virus Diseases / immunology*