Generation of CD8+ suppressor T cells by protoscoleces of Echinococcus multilocularis in vitro.

Addition of protoscoleces (PSC) of Echinococcus multiocularis suppressed proliferative responses in spleen cells stimulated with concanavalin A (Con A) on day 3 of culture. The suppression was not observed in the spleen cell population depleted of CD8+ cells but observed in the population depleted of CD4+ cells, suggesting the involvement of the CD8+ T cells in the apparent suppression. Indeed, flow cytometry analysis revealed that the proportion of CD8+ cells markedly increased in the Con A cultures containing PSC. Furthermore, when spleen cells were co-cultured with PSC alone, marked increase in the proportion of CD8+ cells as well as B220+ cells was observed. Addition of these increasing CD8+ cells suppressed the proliferative responses of fresh spleen cells stimulated with Con A. These findings suggest that the low responsiveness of spleen cells to Con A on day 3 of culture in the presence of PSC is attributable to an active suppressor mechanism including CD8+ T-suppressor cells generated by stimulation with PSC.

Interleukin-1-dependent mitogenic responses induced by protoscoleces of Echinococcus multilocularis in murine lymphocytes.

Mitogenic effects of protoscoleces (PSCs) of Echinococcus multilocularis on murine lymphocytes were studied. Spleen cells from normal BALB/c mice showed significant proliferative responses when cocultured with PSCs. Proliferative responses were observed in both the T and B cell populations. The PSCs also stimulated cells of the macrophage/monocyte lineage to secrete interleukin-1 (IL-1). Depletion of plastic- and Sephadex G-10-adherent cells from the spleen cell population significantly reduced the proliferative responses to PSCs and the low responsiveness was restored by addition of plastic-adherent cells to these cultures. Furthermore, addition of anti-IL-1 serum to the spleen cell cultures stimulated with PSCs completely suppressed the proliferative responses. These findings demonstrate that the mitogenic effect of PSC on lymphocytes depends on IL-1 secreted by cells of macrophage/monocyte lineage.

Suppression of T-cell proliferation by CD8+ T cells induced in the presence of protoscolices of Echinococcus multilocularis in vitro.

Immunoregulatory influences of protoscolices (PSC) of Echinococcus multilocularis on murine T-lymphocyte functions have been examined in an in vitro system. Proliferative responses of spleen cells stimulated with concanavalin A (ConA) or anti-CD3 monoclonal antibodies were depressed by the addition of PSC. In the presence of PSC, both interleukin-2 (IL-2) production and IL-2 receptor (IL-2R) expression by lymphocytes stimulated with ConA were significantly reduced. However, exogenous IL-2 reconstituted both the ConA-stimulated proliferative responses and IL-2R expression. These findings suggest that PSC of E. multilocularis can suppress lymphoid cell responses via influences on IL-2 production. Indeed, addition of CD(8+)-enriched cells from cultures stimulated with ConA plus PSC to fresh spleen cells showed marked suppression of the ConA responses. IL-2 production as well as IL-2R expression on the spleen cells so treated were suppressed. These findings reveal a suppressive immunologic function induced by E. multilocularis PSC that involves inhibition of IL-2 production and reduction of IL-2R expression. The PSC-induced CD8+ cells appear to play a key role in the suppressive regulation of host immune responses against E. multilocularis.