Induction of T helper cell unresponsiveness to antigen by macrophages from schistosomal egg granulomas. A basis for immunomodulation in schistosomiasis?

Abstract

The present studies were undertaken in an effort to understand the role of mononuclear phagocytes in the regulation of the T cell-mediated granulomatous inflammatory response in experimental murine schistosomiasis mansoni. We report that macrophages from schistosomal egg granulomas did not efficiently stimulate, but rather induced marked proliferative unresponsiveness to Ag in an IL-2-producing, I-Ek-restricted, CD4+ Th cell clone specific for pigeon cytochrome c. The unresponsive state of the T cells was achieved after incubation with granuloma macrophages in the presence of the specific Ag fragment 81-104, but not with either of them independently, and was, similarly, restricted by the I-Ek molecule. Equivalent amounts of peritoneal macrophages from schistosome-infected, but not from normal mice, were also effective in inducing T cell unresponsiveness. We postulate that granuloma macrophages, and potentially other accessory cells in schistosome-infected individuals, are similarly capable of inducing anergy in egg Ag-specific Th cells, and that the resulting inhibited T cell reactivity, which translates into failure of lymphokine secretion and of clonal expansion, represents a major basis of the immunologic down-regulation (immunomodulation) of granulomatous hypersensitivity, characteristically seen in this disease.