INTERLEUKIN-1-BETA DECREASES HLA CLASS-II EXPRESSION ON A GLIOBLASTOMA-MULTIFORME CELL-LINE

Antigens encoded within the major histocompatibility complex (MHC) are not normally expressed in the central nervous system (CNS), but can be induced by treatment with interferon-gamma (IFN-gamma). Other cytokines released during an inflammatory process can potentially influence MHC expression as well. One cytokine of interest is interleukin-1 (IL-1), an immunoregulatory polypeptide that is produced by macrophages and also by cells in the CNS. In this study, the effect of IL-1-beta on MHC expression in a human glioblastoma multiforme cell line, U-105 MG, has been examined. Treatment of U-105 MG with 10 U IL-1-beta/ml for a period of 5 days resulted in a decrease in in constitutive cell surface HLA class II expression and limited the induction of class II by IFN-gamma. This effect was also observed on steady-state levels of class II RNA and could be neutralized with antibodies to IL-1-beta. All class II transcripts examined (HLA-DR, -DQ, and -DP-alpha and beta) were affected. Class I expression was only marginally changed by IL-1-beta-treatment. A minimal concentration of 1 U IL-1-beta/ml was required to reduce class II expression and a kinetics experiment indicated that U-105 MG must be treated for at least 4 days with IL-1-beta for a decrease in class II expression to be observed. This study suggests that IL-1 may play a role in limiting immunoreactivity in the CNS by limiting class II induction.