TY - JOUR
T1 - 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
AU - Giovarelli, Mirella
AU - Musiani, Piero
AU - Modesti, Andrea
AU - Dellabona, Paolo
AU - Casorati, Giulia
AU - Allione, Alessandra
AU - Consalvo, Manuela
AU - Cavallo, Federica
AU - Di Pierro, Francesco
AU - De Giovanni, Carla
AU - Musso, Tiziana
AU - Forni, Guido
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
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M3 - Article
C2 - 7673726
AN - SCOPUS:0029079866
VL - 155
SP - 3112
EP - 3123
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -