TY - JOUR
T1 - Constant TCR triggering suggests that the TCR expressed on intestinal intraepithelial γδ T cells is functional in vivo
AU - Malinarich, Frano H.
AU - Grabski, Elena
AU - Worbs, Tim
AU - Chennupati, Vijaykumar
AU - Haas, Jan D.
AU - Schmitz, Susanne
AU - Candia, Enzo
AU - Quera, Rodrigo
AU - Malissen, Bernard
AU - Förster, Reinhold
AU - Hermoso, Marcela
AU - Prinz, Immo
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
KW - CCL4
KW - Ca-flux
KW - IFN-g
KW - γδ T cells
KW - γδ intestinal intraepithelial lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=78649588502&partnerID=8YFLogxK
U2 - 10.1002/eji.201040727
DO - 10.1002/eji.201040727
M3 - Article
C2 - 21108461
AN - SCOPUS:78649588502
SN - 0014-2980
VL - 40
SP - 3378
EP - 3388
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 12
ER -