Induction of tolerance to a murine fibrosarcoma in two zones of dosage--the involvement of suppressor cells

Abstract

Small size inocula (10(1)-10(3) cells) of cells from a syngeneic methylcholanthrene-induced fibrosarcoma (FSA) induced tolerance when injected s.c. into C3Hf mice. Mice were unable to respond to subsequent challenge with moderate, immunogenic doses of FSA. Tolerance was demonstrated in an in vivo transfer (Winn) assay and an in vitro tumour-specific TH cell assay. Low zone tolerance was associated with the presence of tumour-specific TS cells in the spleen. Moderate size inocula (10(4)-10(6) FSA cells) were immunogenic but larger cell doses (greater than 10(6)) were again tolerogenic. In the high zone, tolerance was associated with both tumour-specific TS cells and non T suppressor cells that were not tumour-specific. These results support the view that immunogenic tumours, as they grow from small cell numbers, might be able to escape host surveillance by specifically tolerizing the immune system. They also suggest that large tumour burdens can interfere with the host's immune response by inducing suppressor cells.