Cell-mediated immunity of experimental brain tumors

Abstract

A brain tumor model was produced by intracerebral inoculation of 104 syngeneic malignant glioma cells induced with 20-methylcholanthrene into the right basal ganglia of C57BL/6 mice. Mean survival days of this model was 22.8 ± 3.1 days. Brain tumors were visible on Day, 12 after tumor inoculation and comprized 37 percent of the brain weight by Day 22. The results were as follows. (1) Body weight decreased gradually from Day 15 after tumor inoculation. Spleen and thymus weight, and the number of white blood cells and lymphocytes were reduced from Day 17. Mild splenomegaly was observed on Day 12. (2) Lymphocyte proliferative responses to phytohemagglutinin (PHA) of spleen cells from tumor-bearing mice were impaired from Day 12 and suppressed remarkably on Day 22. When serum from tumor-bearing mice was added to lymphocyte culture medium, blastogenesis of normal spleen cells was also impaired from Day 12 and remarkably suppressed on Day 22. (3) Natural cytotoxic activities of spleen cells and brain mononuclear cells from normal mice against malignant glioma cells in a 15 hr 51Cr release assay were recognized. Cytotoxic activities of spleen cells and brain mononuclear cells from tumor-bearing mice in the same assay were enhanced mildly on Day 12 and recognized by Day 22. (4) Natural cytotoxic cells were observed in the adherent cell fraction of brain mononuclear cells, and in both the adherent and nonadherent cell fractions of spleen cells. It is suggested that changes of cell-mediated immunity appeared at a relatively early stage in tumorbearing mice, although weight loss of organs, leukopenia, and lymphopenia were observed at the terminal stage. Nonspecific activity of lymphocytes was apparently suppressed with the growth of the tumor, as demonstrated by the appearance of serum blocking factor and lymphopenia. Natural cytotoxicity mediated in part by macrophages was maintained even in the terminal stage.