Title: IFN gamma-Induced MHC Class II Expression on Islet Endothelial Cells Is an Early Marker of Insulitis but Is Not Required for Diabetogenic CD4(+) T Cell Migration
Authors: Scott, NA
Zhao, YX
Krishnamurthy, B
Mannering, SI
Kay, TWH
Thomas, HE
Issue Year: 2018
Series Front. Immunol.:
Abstract Diabetogenic T cells infiltrate the pancreatic islets by transmigrating across the microcapillaries residing close to, or within, the pancreatic islets. Deficiency in IFN gamma signaling prevents efficient migration of T cells into the pancreatic islets, but the IFN gamma-regulated molecules that mediate this are uncertain. Homing of autoreactive T cells into target tissues may require antigen specificity through presentation of cognate antigen by MHC expressed on the vascular endothelium. We investigated the hypothesis that IFN gamma promotes the migration of islet antigen-specific CD4(+) T cells by upregulating MHC class II on islet endothelial cells (IEC), thereby providing an antigen-specific signal for islet infiltration. Upon IFN gamma stimulation, MHC class II, which is not constitutively expressed on IEC, was induced. IFN gamma-dependent upregulation of MHC class II was detected in IEC isolated from prediabetic NOD mice at the earliest stages of insulitis, before other markers of inflammation were present. Using a CD4(+) T cell-mediated adoptive transfer model of autoimmune diabetes we observed that even though diabetes does not develop in recipient mice lacking IFN gamma receptors, mice with MHC class II-deficient IEC were not protected from disease. Thus, IFN gamma-regulated molecules, but not MHC class II or antigen presentation by IECs is required for the early migration of antigen-specific CD4(+) T cells into the pancreatic islets.
URI: https://publications.svi.edu.au/publications/4195
Other Identifiers 10.3389/fimmu.2018.02800
Publication type Article