Regulation of the cytotoxic lymphocyte response by macrophage migration inhibitory factor

Abstract

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.

Description

field of invention [0001] The present invention relates to CD4 + and / or CD8 + Regulate (enhance or reduce) the response of cytotoxic lymphocytes to antigens such as tumor-associated antigens by reducing or increasing the level of macrophage migration inhibitory factor (MIF) before, during or after contact between T lymphocytes and antigens Methods and compositions of the reaction. The present invention also relates to compositions and methods for the prevention and treatment of diseases, especially tumors, by modulating the response of cytotoxic lymphocytes to antigens by means of cell-based immunotherapy. technical background [0002] Data from both laboratory studies and human clinical trials indicate that tumor-associated antigens are sufficient to elicit antitumor cytotoxic lymphocyte (CTL) responses that lead to significant tumor regression (27, 28). In some instances, enhancing CTL cytotoxic activity using a cell-based immunotherapeutic strategy (peptide immunizatio...

AI Technical Summary

Problems solved by technology

The mechanisms by which these cytokines inhibit the lytic

Images