Cellular Immunity to Encephalitogenic Factor as Measured by Macrophage Migration Inhibition During Tumour Induction and Growth

Spleen-cell sensitivity to encephalitogenic factor (EF) was measured with the macrophage migration inhibition (MMI) test over a period of time in hamsters inoculated with SV40-transformed tumour cells and in rats treated with 4-dimethylamino-3′-methylazobenzene. Spleen cells from hamsters receiving 10 or 10(3) SV40 tumour cells gave inhibition of macrophage migration with EF at a significance level of P<0·05 21 days after implantation. Spleen cells from animals receiving 10(5) tumour cells gave inhibition at a significance level of P<0·001 after the same interval. Spleen-cell sensitivity to EF, and the abrogation of this sensitivity by serum, was investigated over a period of time in rats undergoing hepatocarcinogenesis. Sensitivity to EF was seen in 2/10 animals (20%) with minimal lesions of the liver, in 2/16 animals (12%) with proliferative changes and/or cholangiofibrosis, in 7/15 animals (46%) with dysplastic lesions of portal-tract epithelial cells and in all 5 animals with cholangiocarcinoma. None of a control group of 10 animals showed any response to EF. Autologous serum abrogated the spleen-cell response to EF in one sensitized animal with proliferative changes and cholangiofibrosis, in all 7 sensitized animals with dysplastic hepatic lesions and in 4/5 sensitized animals with cholangiocarcinoma. Autologous serum had no effect on macrophage migration in the 10 control animals. These findings indicate that a progressive increase in sensitization to EF occurs during carcinogenesis and is evident at the point of preneoplastic dysplasia. This has an obviously important bearing on the clinical use of such tests. IMAGES: