METHODS AND COMPOSITIONS FOR MODULATING REGULATION OF THE CYTOTOXIC LYMPHOCYTE RESPONSE BY MACROPHAGE MIGRATION INHIBITORY FACTOR

摘要

Regulation of expression of CTL activity by macrophage migration inhibitory factor (MIF) is disclosed. In a mouse model using the EL4 tumor, cultured splenocytes from tumor-primed mice secrete high levels of MIF following antigen stimulation in vitro . Parallel splenocytes treated with neutralizing anti-MIF mAb showed a significant increase in CTL response against tumor cells compared to control mAb-treated cultures, with elevated expression of IFN gamma . Histology of tumors from anti-MIF treated animals showed increases in infiltration of both CD4<+> and CD8<+> T cells, as well as apoptotic tumor cells, consistent with observed augmentation of CTL activity in vivo by anti-MIF, which was associated with enhanced expression of the common gamma c chain of the IL-2 receptor that mediates CD8<+>T cell survival. CD8<+> cells of anti-MIF treated tumor-bearing mice showed increased migration into tumors of control mice. Methods for enhancing a CTL response by inhibition of MIF are disclosed.