In the presence of dexamethasone, gamma interferon induces rat oligodendrocytes to express major histocompatibility complex class II molecules.

Abstract

Cells that express major histocompatibility complex (MHC) class H molecules can interact directly with CD4 T lymphocytes and either activate immune actions or become the targets of T-cell-mediated cytotoxic attack. Using rat optic nerve cultures combined with immunocytochemistry and in situ hybridization, we have shown that oligodendrocytes, the major myelin-forming cells of the central nervous system and the main casualty of the immune attacks asated with multiple sclerosis and experimental allergic encephalomyelitis, can be readily induced to express MHIC class II mRNA and surface antigens in vito by exposure to y interferon, provided the glucocorticoid dexamethasone is included in the culture medium. Oligodendrocytes exposed to v interferon without dexamethasone fail to express MHC class H molecules, which may account for the failure of previous attempts to induce expression in these cells. In the central nervous system (CNS), the major conditions of this type are multiple sclerosis and experimental allergic encephalomyelitis (EAE). In the normal CNS, cells express MHC class II molecules at low levels, if at all (4). During immunological assault, such as in multiple sclerosis or EAE, MHC class II expression is seen in association with invading monocytes/macrophages and on microglia, which are endogenous to the brain parenchyma but originate from the monocyte/macrophage lineage (4-6). Neurons themselves are considered unable to express MHC class II molecules, and the only macroglial cells implicated in antigen presentation under these circumstances are astrocytes (5-9). These cells and perinatal 0-2A progenitor cells can also be induced to express MHC class II molecules in response to y interferon (IFN-y) in vitro (4,7,(10)(11)(12). In the peripheral nervous system, IFN-y also induces MHC class II expression on Schwann cells, the glial cells of peripheral nerves (13,14). This effect may be of particular relevance in immune-related diseases, such as leprosy (15) Recombinant rat IFN-y and mouse anti-rat IFN-'y antibody (DB1) were provided by P. Van der Meide (24)

Oligodendrocyte‐microglia cross‐talk in the central nervous system

“…That oligodendrocytes express MHC class I molecules, and so can be targeted by CD8 + T cells, was already described in the 1990s . These findings were initially controversial, but it was subsequently clarified that IFN‐γ treatment induces MHC class I expression on oligodendrocytes in vitro , supporting the idea that the presence of IFN‐γ in demyelinating disorders such as MS may render oligodendrocytes susceptible to MHC class I‐dependent cell death in disease .…”

Glucocorticoids and Central Nervous System Inflammation

“…Synergistic effects between GCs and IL-1 and IL-6 have also been observed in human B cells, potently inducing the production of IgG and IgM (Emilie et al, 1988). Other biological responses to a variety of cytokines such as IL-2 (Fernandez-Ruiz et al, 1989), Interferon (INF)-γ (Bergsteindottir et al, 1992) and granulocyte colony-stimulating factor (G-CSF) are also enhanced in the presence of GCs.…”

Lame Ducks or Fierce Creatures? - The Role of Oligodendrocytes in Multiple Sclerosis

“…Under normal conditions, MHC expression in the CNS does either not occur or is below detection levels (Redwine et al 2001). In vitro experiments showed, however, that oligodendrocytes can be induced to express MHC class I (Grenier et al 1989;Kim 1985) and MHC class II molecules (Bergsteindottir et al 1992). Also in vivo, it has been shown that oligodendrocytes are expressing MHC class I molecules in a murine model of CNS inflammation and demyelination (Redwine et al 2001) and in MS lesions (Hoftberger et al 2004).…”