During many chronic viral infections, the stromal cells of secondary lymphoid organs (SLO), essential to lymphocyte migration, activation, and survival, are disrupted, suggesting abrogation of necessary immune cell interactions. Little is known why and how these changes occur. To study the changes in these scarce stromal populations, we immortalized fibroblastic reticular cells (FRCs), which are stromal cells of T cell zones that are targeted by multiple viruses, and tested the effect of type I and II interferon (IFN). In reaction to IFN-γ, FRCs expressed MHC II, along with co-stimulatory ligands, and activated naïve CD4+ and CD8+ T cells but limited expansion of effector T cells. To IFN-I, interestingly, FRCs responded differentially, upregulating PD-L1 and MHC I in reaction to IFN-β but not IFN-α. To assess the effect of IFN-I on stromal cells, including FRCs, we blocked IFN-I signaling during persistent lymphocytic choriomeningitis virus infection in mice. Surprisingly, IFN-I blockade protected from the SLO destruction that occurs with chronic infection. FRC structure and T cell (and B cell) zones remained intact despite higher viral load and greater numbers of anti-viral T cells. IFN blockade increased FRC expression of T cell/DC chemokines, resulting in significant differences in naïve T cell homing. These data suggest that IFN-I signaling alters lymphocyte migration via stromal cells and regulates pathways that are involved in maintaining SLO architecture.
- Copyright © 2013 by The American Association of Immunologists, Inc.