Killing of metacestodes by normal or post-infection macrophages and the regulation of this activity by cytokines were studied in vitro. The protoscolecidal activity of normal macrophages against Echinococcus granulosus was inhibited by a product of naive T-enriched lymphocytes co-cultured with protoscoleces (PSC). By contrast, supernates from co-cultures of Mesocestoides corti tetrathyridia (MCT) and T-enriched or B-enriched normal lymphocytes increased killing of MCT by normal macrophages. Larvicidal activity (against both PSC and MCT) was enhanced by high concentrations of macrophage-activating factors produced by Con A-stimulated rat lymphocytes (Con A-LK), but was reduced by low concentrations of these factors. Activation by synergism between Con A-LK and recombinant interferon-gamma(r. IFN-gamma) was demonstrated in macrophage-mediated killing of MCT at high effector to target ratio. Cytokine-activation of normal or post-MCT infection macrophages was compared. Macrophages from both 8 and 20 week post-infection mice were refractory to lymphokines from lymphocyte-MCT cultures and displayed greatly reduced killing of MCT. Macrophage activation by Con A-LK and r.IFN-gamma was also impaired, implying a general defect in the ability of these post-infection macrophages to respond to macrophage activating signals. The data indicate that two different mechanisms may exist by which metacestodes regulate potentially larvicidal effector mechanisms. E. granulosus can elicit the production of lymphokines suppressive for PSC killing, whereas M. corti appears directly to induce a refractory state in effector macrophages.

The reaction of Balb/c mice to primary and secondary subcutaneous infection with Echinococcus granulosus protoscoleces (PSC) is described. From 3 to 14 days following primary exposure to PSC, draining lymph nodes increase in weight and there is expansion of T and B lymphocyte populations, enhancement of in vitro lymphocyte transformational responses and production of PSC-specific IgM and IgE antibodies. Despite the persistence of viable PSC in host tissues, lymphocyte responses decline to pre-infection values over the period 3-8 weeks post-infection. Secondary exposure to PSC immediately induces lymphoproliferation, enhancement of transformational responses, production of IgE antibody and encapsulation of PSC by inflammatory cells. Although specific antibody levels remain high until at least 8 weeks after challenge infection, lymphocyte activity begins to decline after 4 days and is profoundly suppressed by 10 days. Parasite viability appears to be significantly reduced in secondary, as opposed to primary, infection and is associated with the accumulation of large numbers of eosinophils, mast cells and macrophages in infected tissues.

Peritoneal macrophages from Mesocestoides corti-infected mice showed a marked and progressive loss of ability to act as accessory cells for syngeneic Con A-stimulated mesenteric lymph node lymphocytes. The same effect on the macrophages could be induced by intraperitoneal injection of M. corti culture supernatant, despite a concurrent increase in numbers of peritoneal adhesive macrophages. The findings are used to compare and contrast the known immunomodulatory effects of M. corti and taeniid metacestodes, the latter differing chiefly in their potential for modifying T-cell as well as macrophage behaviour.

Two models of intraperitoneal infection with E. granulosus equinus by protoscolices and by cyst passage in BALB/c mice were used to provide mesenteric lymph node cells for adoptive cell transfer into syngeneic recipient normal responder mice. The cell transfer inocula were shown to have depleted Thy-1 cells, but to be highly suppressive to the normal sheep erythrocyte response of the recipients. The nature of the depletion and non-specific suppression, and the infectious nature of the latter, are discussed in relation to other examples of mitogenic stimulation resulting in non-specific T cell suppressor activity. The functions of Ly-2,3+ cells, not only as suppressor, but as alloreactive cytotoxic cells, are discussed as a possible, autoimmune explanation for the longevity of the parasite within the mouse model, in contradistinction to the predictable early rejection of analogous xenografts.

Culture of murine lymph node cells together with living protoscolices of Echinococcus granulosus is described. The presence of the parasite induced potent blastic transformation in lymphocytes of unimmunized mice as indicated by tritiated thymidine incorporation. The response was markedly reduced by killing the parasite immediately prior to culture. No blastogenic activity was detectable in supernatants from living parasites cultured alone. Protoscolices from artificially infected syngeneic mice were effective stimuli, as were protoscolices from naturally infected horse and sheep. Stimulation was not detectably reduced by maintenance of the parasite in vitro for 72 h at 37 degrees C or for 46 days at 4 degrees C prior to culture. It is concluded that unprimed lymphocytes are stimulated to transform by surface contact with a stimulator synthesized, but not secreted, by the parasite. The biological significance of the reaction and its possible contribution to immunosuppression are discussed.