Regulation of the CTL response by macrophage migration inhibitory factor

R. Abe, T. Peng, J. Sailors, R. Bucala, C. N. Metz

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Macrophage migration inhibitory factor (MIF) has been shown to be a pivotal cytokine that mediates host inflammatory and immune responses. Recently, immunoneutralization of MIF has been found to inhibit tumor growth in mice; however, the contributing mechanisms underlying this effect have not been well defined. We investigated whether MIF plays a regulatory role in the expression of CTL activity. In a mouse model of the CTL response using the OVA-transfected tumor cell line EL4 (EG.7), we found that cultures of splenocytes obtained from EG.7-primed mice secrete high levels of MIF following Ag stimulation in vitro. Notably, parallel splenocyte cultures treated with neutralizing anti-MIF mAb showed a significant increase in the CTL response directed against EG.7 cells compared with control mAb-treated cultures. This effect was accompanied by elevated expression of IFN-γ. Histological examination of the EG.7 tumors from anti-MIF-treated animals showed a prominent increase in both CD4+ and CD8+ T cells as well as apoptotic tumor cells, consistent with the observed augmentation of CTL activity in vivo by anti-MIF. This increased CTL activity was associated with enhanced expression of the common γc-chain of the IL-2R that mediates CD8+ T cell survival. Finally, CD8+ T lymphocytes obtained from the spleens of anti-MIF-treated EG.7 tumor-bearing mice, when transferred into recipient tumor-bearing mice, showed increased accumulation in the tumor tissue. These data provide the first evidence of an important role for MIF in the regulation and trafficking of anti-tumor T lymphocytes in vivo.

Original languageEnglish (US)
Pages (from-to)747-753
Number of pages7
JournalJournal of Immunology
Volume166
Issue number2
DOIs
StatePublished - Jan 15 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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