Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Encephalitogenic T cells appear capable of destroying class II major histocompatibility complex (MHC) antigen (Ia)-positive glial cells in the brain, thus accounting for the pathologic activity of these lymphocytes in experimental autoimmune encephalomyelitis (EAE). However, glial cells do not generally express Ia molecules, suggesting that regulation of Ia expression figures prominently in autoimmune diseases of the central nervous system. In studies to understand the regulatory mechanisms involved in Ia expression, a glial cell clone generated from the brains of neonatal Lewis rats (F10 clone) readily expressed class II major histocompatibility (Ia) antigens after stimulation by interferon-gamma (IFN-gamma) at doses from 10 to 100 units/ml. Level of the antigen decreased gradually within 5-7 days after cultures were depleted of the cytokine. Reexposure of the cells to the IFN-gamma at 100-fold lower doses induced a stronger Ia response than did the initial exposure. F10 cells also expressed Ia when they were cultured with small numbers of syngeneic T lymphocytes, either proliferating or nonproliferating. Proliferating T cells had direct Ia-inducing activity, whereas nonproliferating T cells had this effect only when they were added to cultures with small amounts of T cell-specific antigen. Moreover, Ia-inducing effects of IFN-gamma on F10 cells were also greatly enhanced when these cells were preexposured to T cells. Our results suggest that initial exposure to IFN-gamma or T cells enhances the Ia responsiveness of glial cells to further stimulation with the cytokine.
 ...
PMID:Enhanced interferon-gamma-induced Ia-antigen expression by glial cells after previous exposure to this cytokine. 191 26

The encephalitogenic potential of a segment of myelin basic protein in experimental autoimmune encephalomyelitis is not always mirrored by the ability of the peptide to mediate in vitro activation of encephalitogenic T cells. Recent studies from our laboratory have demonstrated that the responsiveness of Ag-specific T cells in experimental autoimmune encephalomyelitis is determined not exclusively by Ag but also by the nature of the APC. By varying APC during the in vitro selection of T cells, we could generate distinct sets of rat encephalitogenic T cells, as evidenced by the diversity of TCR usage. Here we establish the importance of APC in the activation of rat encephalitogenic T cells by myelin basic protein peptides. Peptides 69-84-Gly and (P80)68-86, which lacked stimulatory activity toward many encephalitogenic T cells in our proliferation assay when standard APC were used, become strongly stimulatory in the presence of less commonly used APC, i.e., an Ia+ T cell clone (LOA) or an Ia-inducible rat glial cell clone (F10). Nonstimulatory APC failed to activate encephalitogenic T cells even when major cytokines were added, suggesting that these cytokines are not among the factors limiting the activating potential of the APC. Thus, whether or not an immunocompetent T cell can be activated by a given Ag in an autoimmune response may be determined by the properties of APC. This finding has implications for current research efforts to identify pathogenic self proteins.
 ...
PMID:Major role of antigen-presenting cells in the response of rat encephalitogenic T cells to myelin basic proteins. 768 28

Unbiased identification of susceptibility genes might provide new insights into pathogenic mechanisms that govern complex inflammatory diseases such as multiple sclerosis. In this study we fine mapped Eae18a, a region on rat chromosome 10 that regulates experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. We utilized two independent approaches: (1) in silico mapping based on sequence similarity between human multiple sclerosis susceptibility regions and rodent EAE quantitative trait loci and (2) linkage mapping in an F10 (DA x PVG.AV1) rat advanced intercrossed line. The linkage mapping defines Eae18a to a 5-Mb region, which overlaps one intergenomic consensus region identified in silico. The combined approach confirms experimentally, for the first time, the accuracy of the in silico method. Moreover, the shared intersection between the results of both mapping techniques defines a 1.06-Mb region containing 13 candidate genes for the regulation of neuroinflammation in humans, rats, and mice.
 ...
PMID:Definition of a 1.06-Mb region linked to neuroinflammation in humans, rats and mice. 1662 98