Production of tumor necrosis factor-α as a result of glia-T-Cell interaction correlates with the pathogenic activity of myelin basic protein-reactive T cells in experimental autoimmune encephalomyelitis
✍ Scribed by D. Sun; X. Hu; R. Shah; L. Zhang; C. Coleclough
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 956 KB
- Volume
- 45
- Category
- Article
- ISSN
- 0360-4012
No coin nor oath required. For personal study only.
✦ Synopsis
Tumor necrosis factor-a (TNF-a) 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-a 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-a mRNA. TNF-a 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-a 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-a 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-a was shown to have direct cytotoxic effect on glial cells, which was greatly enhanced by small amounts of interferon-? (IFN-y).