Constant TCR triggering suggests that the TCR expressed on intestinal intraepithelial γδ T cells is functional in vivo

Frano H. Malinarich, Elena Grabski, Tim Worbs, Vijaykumar Chennupati, Jan D. Haas, Susanne Schmitz, Enzo Candia, Rodrigo Quera, Bernard Malissen, Reinhold Förster, Marcela Hermoso, Immo Prinz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Intestinal intraepithelial lymphocytes carrying the γδ TCR (γδ iIEL) are involved in the maintenance of epithelial integrity. γδ iIEL have an activated phenotype, characterized by CD69 expression and increased cell size compared with systemic T lymphocytes. As an additional activation marker, the majority of γδ iIEL express the CD8αα homodimer. However, our knowledge about cognate ligands for most γδ TCR remains fragmentary and recent advances show that γδ T cells including iIEL may be directly activated by cytokines or through NK-receptors, TLR and other pattern recognition receptors. We therefore asked whether the TCR of γδ iIEL was functional beyond its role during thymic selection. Using TcrdH2BeGFP (Tcrd, T-cell receptor δ locus; H2B, histone 2B) reporter mice to identify γδ T cells, we measured their intracellular free calcium concentration in response to TCR-crosslinking. In contrast to systemic γδ T cells, CD8αα+ γδ iIEL showed high basal calcium levels and were refractory to TCR-dependent calcium-flux induction; however, they readily produced CC chemokine ligand 4 (CCL4) and IFN-γ upon TCR triggering in vitro. Notably, in vivo blocking of the γδ TCR with specific mAb led to a decrease of basal calcium levels in CD8αα+ γδ iIEL. This suggests that the γδ TCR of CD8αα+ γδ iIEL is constantly being triggered and therefore functional in vivo.

Original languageEnglish
Pages (from-to)3378-3388
Number of pages11
JournalEuropean Journal of Immunology
Volume40
Issue number12
DOIs
StatePublished - Dec 2010
Externally publishedYes

Keywords

  • CCL4
  • Ca-flux
  • IFN-g
  • γδ T cells
  • γδ intestinal intraepithelial lymphocytes

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