Murine gamma delta intraepithelial lymphocyte response to type I IFN and TCR blockade

Interferon alpha (IFNa) is a pro-inflammatory cytokine that is rapidly upregulated as part of an innate immune response. Gamma delta intraepithelial lymphocytes (gd IEL) mount a rapid antimicrobial response to luminal microorganisms and previous report indicate that the T cell receptor (TCR) of these cells is constantly triggered at steady-state. We assessed the contribution of tonic TCR activation in response to acute, systemic IFNa administration among murine gd IELs. Our data demonstrate that inhibiting basal TCR signaling has a minimal effect on the transcriptional profile of gd IELs and acute IFNa exposure induces antiviral gene programs independent of TCR signaling. Mice were treated mice with 200 ug TCRgd antibody (UC7-13D5) or Armenian hamster IgG i.p. (-48 or -24 h) prior to i.v. administration with 1 ug murine IFNa or phosphate buffered saline (PBS) for 5 h. RNAseq was performed on sorted gd IELs isolated from murine small intestine from each of the following treatment groups: IgG-PBS, IgG-IFNa, UC713D5-PBS, UC713D5-IFNa