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

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.

Morphological and biochemical alterations of macrophages produced by a glycan, PSK.

A glycan extracted from Coriolus versicolor (PSK, Krestin) which has antitumor and immunomodulator properties produced marked morphological and biochemical changes when added to cultures of mouse peritoneal macrophages. The cells were more spread and elongated than in control cultures, and these changes were accompanied by alterations in the rate of protein and DNA synthesis. In PSK-treated murine peritoneal macrophages the rate of protein synthesis increased above the level seen in control cultures after two days and reached a level twenty-fold higher than control on day four; this elevated rate of protein synthesis was maintained throughout the seven-day observation period. DNA synthesis was induced after four days in the presence of PSK, and reached a level ten-fold higher than control baseline on day five. This induction of DNA synthesis, however, could not be attributed to a mitogenic activity on lymphocytes. The alterations caused by PSK in macrophage metabolism may be related to the immunomodulating and antitumor activities of PSK in vivo.

Abnormal expression of complement receptor (CR1) in IgA nephritis: increase in erythrocytes and loss on glomeruli in patients with impaired renal function.

The number of complement receptor for C3b (CR1) molecules in erythrocytes from patients with renal diseases was measured by an immunoradiometric assay using monoclonal antibodies against CR1. IgA nephritis patients with high serum creatinine value (Scr) showed markedly elevated levels of CR1, whereas patients with normal Scr had normal CR1 levels. A similar increase in CR1 number was observed in membranoproliferative glomerular nephritis with high Scr. CR1 of these patients functioned normally as a cofactor of C3b inactivator in cleaving immune complex-bound C3b. In contrast, a high frequency (5/6) of negative staining of glomerular CR1 was observed in IgA nephritis patients with high Scr by immunofluorescence study. We postulate that the disease-associated, acquired factors at least in part contribute to the abnormal expression of CR1: elevated levels in erythrocytes and defective expression on glomeruli.