title: Production of tumor necrosis factor-alpha as a result of glia-T-cell interaction correlates with the pathogenic activity of myelin basic protein-reactive T cells in experimental autoimmune encephalomyelitis.
abstract: Tumor necrosis factor-alpha (TNF-alpha) has attracted the greatest attention as a major factor in experimental autoimmune encephalomyelitis (EAE) pathogenesis. We compared rats undergoing EAE with manipulated but healthy animals by examining TNF-alpha gene expression in cells recovered from the brain. We used reverse transcriptase-polymerase chain reaction (RT-PCR) as a sensitive assay for detection and Northern blot hybridization as a reliable quantitative assay of TNF-alpha mRNA. TNF-alpha gene expression was consistently detected in rats immunized with myelin basic protein (MBP) emulsified in complete Freund adjuvant (CFA), but not in rats immunized with MBP emulsified in incomplete Freund adjuvant (IFA), which does not induce EAE. Similarly, brain-derived cells from rats injected with cloned encephalitogenic T cells contained increased amounts of TNF-alpha mRNA compared with rats injected with nonencephalitogenic T cell clones similar in antigen specificity and in vitro lymphokine-producing capacity. Considering that the differing pathogenic capacity of MBP-reactive T cells might result from differing patterns of interaction with glia, we examined the impact of T-cell-glia interaction in vitro on cytokine gene expression in both cell types. Glial components were efficient in inducing TNF-alpha expression in T cells; T cells and T-cell-derived cytokines could elicit expression of several lymphokine genes in glial cells. Comparison of RT-PCR and blot hybridization assays, however, suggested that cytokine expression was much more efficient, on a per cell basis, in T cells than in glia. TNF-alpha was shown to have direct cytotoxic effect on glial cells, which was greatly enhanced by small amounts of interferon-gamma (IFN-gamma).
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.forename: R
authors.initials: R
authors.lastname: Shah
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Coleclough
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line / Q000737:chemistry / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002490:Central Nervous System / Q000166:cytology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006168:Guinea Pigs; D007371:Interferon-gamma / Q000494:pharmacology; D004676:Myelin Basic Protein / Q000032:analysis; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000494:pharmacology
chemical_list: D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma