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

Tumor necrosis factor-alpha (TNF-alpha) has attracted the greatest att ention as a major factor in experimental autoimmune encephalomyelitis (EAE) pathogenesis, We compared rats undergoing EAE with manipulated b ut healthy animals by examining TNF-alpha gene expression in cells rec overed 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 wit h myelin basic protein (MBP) emulsified in complete Freund adjuvant (C FA), but not in rats immunized with MBP emulsified in incomplete Freun d adjuvant (IFA), which does not induce EAE, Similarly, brain-derived cells from rats injected with cloned encephalitogenic T cells containe d 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 differi ng patterns of interaction with glia, we examined the impact of T-cell -glia interaction in vitro on cytokine gene expression in both cell ty pes, Glial components were efficient in inducing TNF-alpha expression in T cells; T cells and T-cell-derived cytokines could elicit expressi on of several lymphokine genes in glial cells, Comparison of RT-PCR an d blot hybridization assays, however, suggested that cytokine expressi on was much more efficient, on a per cell basis, in T cells than in gl ia, TNF-alpha was shown to have direct cytotoxic effect on glial cells , which was greatly enhanced by small amounts of interferon-gamma (IFN -gamma). (C) 1996 Wiley-Liss, Inc.