title: Malaria exoantigens induce T-independent antibody that blocks their ability to induce TNF.
abstract: Much of the pathology of malaria may be due to the interactions of cytokines, especially tumour necrosis factor (TNF), with various cell types, including endothelial cells, with consequent widespread systemic effects. It has been shown previously that heat-stable exoantigens in the supernatants of blood-stage parasite cultures induced the release of TNF in vitro from activated macrophages and behaved like toxins in vivo, that mice immunized with the antigens are protected from the toxic effect and that their serum specifically blocks the ability of the antigens to stimulate the production of TNF. It is reported here that the inhibitory antibody is mainly IgM and that it appears to be T-independent, as the titres of antisera from T-deficient and immunologically intact mice were similar. Antisera raised against exoantigens from two species of rodent parasite inhibited TNF production by those of the human parasite Plasmodium falciparum, and vice versa, indicating that the TNF-inducing moieties of the exoantigens cross-react and therefore presumably contain common epitopes. Thus vaccination with these exoantigens might provide a means of protection against the clinical effects of malaria and of generating anti-disease immunity by reducing cytokine production. However, these findings imply that it will be necessary to confer on these antigens the ability to stimulate T cells and generate memory before they can provide a useful basis for an anti-disease vaccine. The results obtained are discussed in relation to some of the epidemiological features of malaria.
authors.affiliation: Department of Immunology, University College & Middlesex School of Medicine, London.
authors.forename: C A
authors.initials: CA
authors.lastname: Bate
authors.forename: J
authors.initials: J
authors.lastname: Taverne
authors.forename: A
authors.initials: A
authors.lastname: Davé
authors.forename: J H
authors.initials: JH
authors.lastname: Playfair
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000953:Antigens, Protozoan / Q000276:immunology*; D000955:Antigens, T-Independent / Q000276:immunology*; D001667:Binding, Competitive; D003429:Cross Reactions; D005260:Female; D007106:Immune Sera / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D010961:Plasmodium / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000955:Antigens, T-Independent; D007106:Immune Sera; D007075:Immunoglobulin M; D014409:Tumor Necrosis Factor-alpha