Possible role of macrophage-like suppressor cells in the anti-tumour activity of BCG

Abstract

Summary.-The i.v. injection of high doses (3 mg) of BCG into C3H mice bearing a transplantable 3-methylcholanthrene-induced fibrosarcoma caused the regression of a significant proportion. This effect was most evident when the BCG was injected on the day of the graft, or 7 days later. The injection of this agent either 14 days before the graft, or in low doses (0.1 or 0 5 mg), or directly into the tumour (i.t.) only prolonged the survival of the animals. Spleen cells from systemic high-dose BCGtreated mice were found to exert a strong nonspecific cytostatic effect in vitro that was not an artefact of the test conditions, and was not expressed by cells from lowdose animals. The cytostatic effect was shown to be caused by cells with the characteristics of macrophages, i.e. they were strongly adherent, unaffected by treatment with anti-Thy 1.2 + C', radioresistant but heat-sensitive, and were detected in BCG-treated "B" mice.The spleens of high-dose BCG-treated mice also contained suppressor cells that were capable of inhibiting the in vitro reactivity of normal T cells to PHA. Like the cytostatic effect, this suppressor activity was not detected in low-dose mice, and the cells responsible had the properties of macrophages; the effect was lost after the removal of adherent cells by sequential exposure to plastic and colloidal iron, but was conserved after treatment with anti-Thy 1.2 + C'. T-cell-deprived animals, such as "B" or nude mice, also developed suppressor-cell activity when treated with systemic high-dose BCG.Close parallels became evident between the in vivo anti-tumour activity of BCG, the in vitro cytostatic effect, and the suppressor-cell activity. We here discuss the possible role of suppressor cells in the mechanism of action of this agent.

Studies on the Development of Tuberculin Sensitivity in Immunized Guinea Pigs with Demonstration of a Close Relationship between Results of Skin Tests and the Lymphocyte Transformation Technique

“…In a recent paper we have demon strated that the interpretation of the effect of addition of 2-mercaptoethanol and mycostatin to the LT cul ture medium is highly dependent on this choice [10], The observation in the present study that the values of the control cultures vary with the duration of immuni zation emphasizes the problem. Such a stimulation of controls at a phase of the immune reaction where ac tivity is high has previously been reported in guinea pigs [14,21,22,26], mice [3] and man [6,19], but has not been analyzed in relation to different methods of expressing results of LT testing.…”