Local release of IL-10 by transfected mouse mammary adenocarcinoma cells does not suppress but enhances antitumor reaction and elicits a strong cytotoxic lymphocyte and antibody-dependent immune memory

Mirella Giovarelli, Piero Musiani, Andrea Modesti, Paolo Dellabona, Giulia Casorati, Alessandra Allione, Manuela Consalvo, Federica Cavallo, Francesco Di Pierro, Carla De Giovanni, Tiziana Musso, Guido Forni

Research output: Contribution to journalArticlepeer-review

Abstract

The cDNA coding for mouse IL-10 (mIL-10) was transduced into the parental cells of a spontaneous adenocar-cinoma of BALB/c mice (TSA-pc), and clones secreting small, medium, and large quantities of IL-10 were selected. In vivo, both low and high producer clones do not display an enhanced ability to grow in H-2 and non-H-2 incompatible mice. Instead, the intensity of their rejection increases in function of the amount of mIL-10 released. After an initial growth period in syngeneic mice, high producer clones undergo complete rejection due to the combined action of CD8+ lymphocytes, NK cells, and neutrophils. After this rejection, mice are immune to a subsequent challenge with TSA-pc. This memory rests on a strong lytic activity of CD8+ CTL and granulocytes. Following the rejection, mice also develop anti-TSA Ab that guide the granulocytes in TSA-pc memory reaction. A direct comparison shows that although TSA clones engineered to release IL-2 activate CTL and no anti-TSA Ab, those engineered to release IL-4 activate a strong Ab response but not CTL. The kind of cytokine released by the tumors appears to determine the type of response. However, IL-10 high producer cells do not deviate the immune memory, neither toward a Th1 nor a Th2. Both the CTL activity and the Ab responses induced by IL-10 high producer cells are the strongest so far observed in the TSA system.

Original languageEnglish
Pages (from-to)3112-3123
Number of pages12
JournalJournal of Immunology
Volume155
Issue number6
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Immunology

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