Development of cell-mediated antiviral immunity and macrophage activation in C3H/HeN mice infected with mouse mammary tumor virus.

Abstract

Spontaneous immunologic reactivity to MW, maerophage-mediated cytotoxicity against tumor cells, and the level of lymphoproliferative responses to mitogens were investigated in normal virgin C3H/HeN female mice infected (C3H+) or uninfected (C3H-) with oncogenic MTV. Spleen cells from C3H+ mice, 14 to 20 weeks of age, produced migration-inhibitory factor (MIF) upon in vitro stimulation with MTV. In contrast, reactivity was never seen with spleen cells of C3H- mice of any age. Spleen cells of 14-week-old C3H+ mice also spontaneously produced MIF' upon in vitro incubation, indicating that an in vivo activation by MW may have occurred. Age-related differences between C3H+ and C3H- mice were also reflected by other measures of cell-mediated immune reactivity. Unstimulated peritoneal macrophages from 14- to 20-week-old C3H+ mice were significantly more cytotoxic for tumor cells than macrophages from younger or older C3H+ mice or from C3H- mice of any age, whereas no difference in the NK activity of spleen cells from 6- to 38-week-old C3H+ and C3H- mice was observed. In contrast to the MIF' production and increased macrophage cytotoxicity of the 14- to 20-weekold C3H+ mice, their lymphoproliferative responses to the mitogens, PHA, Con A, and LPS, were depressed in comparison to C3H- mice of the same age. This depression was associated with the appearance of suppressor cell activity, with macrophages from 14- to 20-week-old C3H+ mice capable of suppressing the mitogenic response of normal spleen cells. The present results indicate that C3H+ mice spontaneously develop cell-mediated immunity that is accompanied by the activation of macrophages that are both cytotoxic against tumor cells and immunosuppressive.