Deficiency of interleukin-2 production upon addition of soluble egg antigen to cultures of isolated hepatic granulomas or hepatic granuloma cells from mice infected with Schistosoma japonicum

Abstract

Schistosoma japonicum-infected C57BL/6 mice show similar dynamics of hepatic granulomatous inflammation and delayed hypersensitivity elicited by soluble egg antigens (SEA) which reach peak levels at 9 weeks of infection and then spontaneously regress. In an attempt to link the level of interleukin 2 (IL-2) production to the spontaneous regression of hepatic granulomatous inflammation, the study determined the dynamics of IL-2 production by SEA-challenged isolated hepatic granulomas (HG) and cells isolated enzymatically from the HG. The production of IL-2 by SEA-stimulated HG or HG cells reached its peak when these preparations from 9-week-infected mice were stimulated and fell thereafter. Some possible mechanisms that might explain the IL-2 deficiency were examined. This deficiency is not due to the in vitro binding of IL-2 by the HG cells of infected mice and is, therefore, due rather to underproduction of IL-2. The deficiency was also not explained by reduced numbers of antigen-presenting cells (macrophages or B cells) or of L3T4+ T lymphocytes. In vitro SEA-induced IL-2 production by HG cells from acutely infected mice was suppressed consistently by Lyt-2+ T cells from the spleens and in the majority of our experiments by Lyt-2+ T cells from the HG of mice infected for 10 weeks. These findings are consistent with the main features of our working hypothesis, but it remains to be proven that in vivo deficiency of lymphokine(s) such as IL-2 is responsible for the spontaneous decrease in granulomatous inflammation and that this lymphokine deficiency is a result of suppression.