Dysfunction of Ia-positive antigen-presenting cells in tumor-bearing mice.

The activities of T cells and antigen-presenting cells in spleen from tumor-bearing mice were studied in vitro. The in vitro induction of trinitrophenyl (TNP)-specific proliferative T cell responses and TNP-specific cytotoxic T cell responses was markedly impaired in spleen cells from X5563 plasmacytoma-bearing C3H/He mice. The activity of TNP-hapten presentation to proliferative T cells and cytotoxic T cells was also impaired in spleen from tumor-bearing mice. Suppressor macrophage activity was not observed in spleen from tumor-bearing mice, because the addition of TNP-modified spleen cells from tumor-bearing mice to TNP-modified spleen cells from normal mice did not suppress the activity of TNP-hapten-presenting cells from normal mice and the addition of indomethacin, an inhibitor of prostaglandin synthesis, to the culture of T cells with TNP-modified spleen cells from tumor-bearing mice did not restore their activity. The population of I-region associated antigen (Ia)-positive cells in spleen macrophages decreased in tumor-bearing mice. Furthermore, the production of interleukin 1 by spleen macrophages was also impaired in tumor-bearing mice. These results suggest that one of the mechanisms leading to immunological abnormality in the tumor-bearing host is mediated by the dysfunction of Ia-positive antigen-presenting cells.