We analyzed the ability of interferon (IFN)-gamma knockout mice (GKO) to reject a colon carcinoma transduced with interleukin (IL)-12 genes (C26/IL-12). Although the absence of IFN-gamma 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 gamma-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-gamma in maintaining the CD8-polymorphonuclear leukocyte cross-talk that is a hallmark of tumor rejection.
Interferon gamma-independent rejection of the interleukin-12-transduced carcinoma cells requires CD4(+) T cells and granulocyte-Macrophage colony-stimulating factor / Zilocchi, C.; Stoppacciaro, Antonella; Chiodoni, C.; Parenza, M.; Terrazzini, N.; Colombo, Mp. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - STAMPA. - 188:(1998), pp. 133-143. [10.1084/jem.188.1.133]
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Titolo: | Interferon gamma-independent rejection of the interleukin-12-transduced carcinoma cells requires CD4(+) T cells and granulocyte-Macrophage colony-stimulating factor. | |
Autori: | ||
Data di pubblicazione: | 1998 | |
Rivista: | ||
Citazione: | Interferon gamma-independent rejection of the interleukin-12-transduced carcinoma cells requires CD4(+) T cells and granulocyte-Macrophage colony-stimulating factor / Zilocchi, C.; Stoppacciaro, Antonella; Chiodoni, C.; Parenza, M.; Terrazzini, N.; Colombo, Mp. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - STAMPA. - 188:(1998), pp. 133-143. [10.1084/jem.188.1.133] | |
Handle: | http://hdl.handle.net/11573/68357 | |
Appartiene alla tipologia: | 01a Articolo in rivista |