REGULATION OF CYTOKINE GENE-EXPRESSION IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

We previously reported that recovery of Lewis rats from experimental a utoimmune encephalomyelitis (EAE) is associated with the appearance of suppressor T cells (Ts), These Ts secrete TGF-beta which downregulate s the production of inflammatory cytokines by the effector T cells tha t mediate this disease, In the present study, we immunized Lewis rats with myelin basic protein (MBP) + CFA, and evaluated purified T cells and MBP-activated spleen cells (SpC) during the paralytic phase (day 1 2) and after recovery (days 30-33) for TGF-beta and interferon (IFN)-g amma mRNA. We used reverse transcriptase-polymerase chain reaction (RT -PCR), quantitated on the basis of beta-actin mRNA, Abundant IFN-gamma mRNA was present in MBP-activated SpC obtained on day 12, In contrast , only trace IFN-gamma mRNA was detected in day 30 activated SpC, and no IFN-gamma mRNA was present in purified, nonactivated T cells obtain ed at either time, The level of IFN-gamma mRNA correlated with secreti on of IFN-gamma as determined by ELISA on SpC culture supernatants, an d with severity of adoptively transferred EAE by the activated SpC, Th us, it appears that IFN-gamma mRNA is both transcribed and translated in response to antigen activation, resulting in secretion of IFN-gamma by the disease-inducing Te. In contrast, when we used RT-PCR to inves tigate the expression of TGF-beta mRNA, we found the transcript presen t in isolated T cells and MBP-activated SpC obtained from rats at both days 12 and 30. The presence of TGF-beta mRNA at time points correspo nding to both clinical EAE and recovery suggests post-transcriptional regulation of the production of this immunoregulatory cytokine. (C) 19 96 Wiley-Liss, Inc.