Mechanisms of activation of innate-like intraepithelial T lymphocytes

Maud Vandereyken, Olivia James, Mahima Swamy (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

17 Citations (Scopus)
134 Downloads (Pure)


Intraepithelial T lymphocytes (T-IEL) contain subsets of innate-like T cells that evoke innate and adaptive immune responses to provide rapid protection at epithelial barrier sites. In the intestine, T-IEL express variable T cell antigen receptors (TCR), with unknown antigen specificities. Intriguingly, they also express multiple inhibitory receptors, many of which are normally found on exhausted or antigen-experienced T cells. This pattern suggests that T-IEL are antigen-experienced, yet it is not clear where, and in what context, T-IEL encounter TCR ligands. We review recent evidence indicating TCR antigens for intestinal innate-like T-IEL are found on thymic or intestinal epithelium, driving agonist selection of T-IEL. We explore the contributions of the TCR and various co-stimulatory and co-inhibitory receptors in activating T-IEL effector functions. The balance between inhibitory and activating signals may be key to keeping these highly cytotoxic, rapidly activated cells in check, and key to harnessing their immune surveillance potential.
Original languageEnglish
Pages (from-to)721-731
Number of pages11
JournalMucosal Immunology
Issue number5
Early online date15 May 2020
Publication statusPublished - 1 Sept 2020


  • Innate-like T cells
  • Intraepithelial lymphocytes
  • T cell antigen receptor
  • co-stimulatory receptors
  • co-inhibitory receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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