| First Author | Malinarich FH | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 12 | Pages | 3378-88 |
| PubMed ID | 21108461 | Mgi Jnum | J:174581 |
| Mgi Id | MGI:5139989 | Doi | 10.1002/eji.201040727 |
| Citation | Malinarich FH, et al. (2010) Constant TCR triggering suggests that the TCR expressed on intestinal intraepithelial gammadelta T cells is functional in vivo. Eur J Immunol 40(12):3378-88 |
| abstractText | Intestinal intraepithelial lymphocytes carrying the gammadelta TCR (gammadelta iIEL) are involved in the maintenance of epithelial integrity. gammadelta 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 gammadelta iIEL express the CD8alphaalpha homodimer. However, our knowledge about cognate ligands for most gammadelta TCR remains fragmentary and recent advances show that gammadelta 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 gammadelta iIEL was functional beyond its role during thymic selection. Using TcrdH2BeGFP (Tcrd, T-cell receptor delta locus; H2B, histone 2B) reporter mice to identify gammadelta T cells, we measured their intracellular free calcium concentration in response to TCR-crosslinking. In contrast to systemic gammadelta T cells, CD8alphaalpha(+) gammadelta 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-gamma upon TCR triggering in vitro. Notably, in vivo blocking of the gammadelta TCR with specific mAb led to a decrease of basal calcium levels in CD8alphaalpha(+) gammadelta iIEL. This suggests that the gammadelta TCR of CD8alphaalpha(+) gammadelta iIEL is constantly being triggered and therefore functional in vivo. |
