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

Abstract

Intestinal intraepithelial lymphocytes carrying the cd TCR (cd iIEL) are involved in the maintenance of epithelial integrity. cd 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 cd iIEL express the CD8aa homodimer. However, our knowledge about cognate ligands for most cd TCR remains fragmentary and recent advances show that cd 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 cd iIEL was functional beyond its role during thymic selection. Using TcrdH2BeGFP (Tcrd, T-cell receptor d locus; H2B, histone 2B) reporter mice to identify cd T cells, we measured their intracellular free calcium concentration in response to TCRcrosslinking. In contrast to systemic cd T cells, CD8aa 1 cd 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-c upon TCR triggering in vitro. Notably, in vivo blocking of the cd TCR with specific mAb led to a decrease of basal calcium levels in CD8aa 1 cd iIEL. This suggests that the cd TCR of CD8aa 1 cd iIEL is constantly being triggered and therefore functional in vivo.

T cell receptor signalling in γδ cell development: strength isn’t everything

“…These cells (j) are probably precursors of IL-17A-producing gd cells from the peritoneal cavity and female reproductive tract (k), dermis (l) and lymph nodes (m). Data are from [7,[9][10][11][12][13][14][15][16][17]20,25,47,48,63].…”

Selection of Self-Reactive T Cells in the Thymus

“…nIEL were recently shown to display high basal calcium levels and be refractory to TCR-dependent calcium-flux induction. Blocking the TCR on γδ+ nIEL in vivo led to a decrease of basal calcium suggesting that γδ+ nIEL, at least, are constantly being triggered through the TCR (70). …”

Innate Immunity Modulation by the IL-33/ST2 System in Intestinal Mucosa

“…Tissue homeostasis is achieved independently of constant exposure to environmental changes. γ / δ T lymphocytes produce keratinocyte growth factor, which stimulates proliferation and differentiation of epithelial cells [125] as well as chemokines involved in T reg recruitment into the lamina propria [126]. …”