Interferon γ-independent rejection of interleukin 12-transduced carcinoma cells requires CD4+ T cells and granulocyte/macrophage colony- stimulating factor

Chiara Zilocchi, Antonella Stoppacciaro, Claudia Chiodoni, Mariella Parenza, Nadia Terrazzini, Mario P. Colombo

Research output: Contribution to journalArticlepeer-review

Abstract

We analyzed the ability of interferon (IFN)-γ knockout mice (GKO) to reject a colon carcinoma transduced with interleukin (IL)-12 genes (C26/IL- 12). Although the absence of IFN-γ impaired the early response and reduced the time to tumor onset in GKO mice, the overall tumor take rate was similar to that of BALB/c mice. In GKO mice, C26/IL-12 tumors had a reduced number of infiltrating leukocytes, especially CD8 and natural killer cells. Analysis of the tumor site, draining nodes, and spleens of GKO mice revealed reduced expression of IFN-inducible protein 10 and monokine induced by γ-IFN. Despite these defects, GKO mice that rejected C26/IL-12 tumor, and mice that were primed in vivo with irradiated C26/IL-12 cells, showed the same cytotoxic T lymphocyte activity but higher production of granulocyte/macrophage colony-stimulating factor (GM-CSF) as compared with control BALB/c mice. Treatment with monoclonal antibodies against GM-CSF abrogated tumor regression in GKO but not in BALB/c mice. CD4 T lymphocytes, which proved unnecessary or suppressive during rejection of C26/IL-12 cells in BALB/c mice, were required for tumor rejection in GKO mice. CD4 T cell depletion was coupled with a decline in GM-CSF expression by lymphocytes infiltrating the tumors or in the draining nodes, and with the reduction and disappearance of granulocytes and CD8 T Cells, respectively, in tumor nodules. These results suggest that GM-CSF can substitute for IFN-γ in maintaining the CDS-polymorphonuclear leukocyte cross-talk that is a hallmark of tumor rejection.

Original languageEnglish
Pages (from-to)133-143
Number of pages11
JournalJournal of Experimental Medicine
Volume188
Issue number1
DOIs
Publication statusPublished - Jul 6 1998

Keywords

  • CD4T lymphocytes
  • Interferon γ
  • Interleukin 12
  • Knockout mice
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology

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