Fetal Exposure to Interferon-y Leads to Induction of Antigen-Presenting Molecules and Leukocyte Recruitment

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Abstract
Embryonic tissue expresses a very low level of MHC molecules, and these few appear only late in ontogeny. Possibly related are deficiencies in the expression of TAP molecules and also the fetus’ need to avoid maternal immunologic rejection. However, the fetus may overcome the lack of Ag-presenting molecules when threatened by inflammation from pathogens that cross the placental barrier. To study embryonic responses to inflammation, we used transgenic mice that express pancreatic IFN-γ (Ins-IFN-y mice). In this unique model, the transgene is expressed well before birth, permitting evaluation of MHC class I, II and TAP-1, -2 expression as well as immunohistological characteristics of pancreatic inflammation. Our results revealed strong positivity for MHC class I and II molecules in the pancreata of Ins-IFN-γ mice beginning at embryonic day (E) 12, but not in those of nontransgenic embryos. TAP-1 and -2 were also evident in transgenic pancreatic tissue beginning at E10 simultaneously with formation of the pancreatic primordium. Interestingly, as early as E14, the transgenic pancreata contained CD4CD8 T lymphocytes and other bone marrow-derived cells such as monocytes. These results suggest that embryos respond to immunological stimuli by producing Ag-presenting molecules and recruiting immature T cells and monocytes.