Deficiency of interleukin-2 activity upon addition of soluble egg antigen to cultures of spleen cells from mice infected with Schistosoma japonicum

Abstract

Schistosomajaponicum-infected C57BL/6 mice show similar dynamics of hepatic granulomatous inflammation (HGI) and delayed hypersensitivity (DH) elicited by soluble egg antigens (SEA) which reach peak levels at 9 weeks of infection and then spontaneously regress. The in vitro SEA-induced proliferation of spleen cells (SC) from infected animals attained its high point and then declined when SC from 5-week-infected mice were used. The present study determined the dynamics of interleukin-2 (IL-2) production by SEA-challenged SC from infected mice in an attempt to link the level of IL-2 production to the spontaneous regression of the aforementioned T-cell-mediated immune responses. The production of IL-2 by SEA-stimulated SC reached its peak when cells from 7-week-infected mice were challenged at least 2 weeks after the peak of the proliferative response, but declined at about the same time as the HGI and DH responses. Therefore, the decline in IL-2 activity cannot alone explain the diminished proliferative response but could account for the reduction in HGI and DH in vivo. 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 SC of infected mice and is, therefore, likely to be due to underproduction of IL-2. Nor is the deficiency explained by reduced numbers of antigen-presenting cells (macrophages and B cells) or of L3T4+ T lymphocytes or by suppression of IL-2 production by macrophages or macrophage products such as prostaglandins. However, suppression of IL-2 production was observed consistently upon coculture of SC from acutely infected mice with SC from mice infected for 10 weeks. The cells which suppress appear to be Lyt2+ T cells. The data are consistent with the hypothesis that suppressor T cells inhibit the production of IL-2 and perhaps of other cytokines or Iymphokines and that this suppression explains the spontaneous down-regulation of HGI which occurs during schistosomiasis japonica.

Schistosoma japonicum-infected mice show reduced hepatic fibrosis and eosinophilia and selective inhibition of interleukin-5 secretion by CD4+ cells after treatment with anti-interleukin-2 antibodies

“…The magnitude and pattern of IL-2 secretion by spleen cells in our experiment are similar to those reported by Stavitsky and Harold, who noted decreased IL-2 secretion by spleen or granuloma cells in chronically infected mice in parallel with decreased blastogenic responses to SEA in these same mice (19,20). Our results, on the contrary, indicate that regulation of granuloma size is unlikely to be wholly attributed to the decreased availability of IL-2 since granulomas were slightly larger at both 7 and 10 weeks in our 4.…”

Release of Interleukin 2 and Gamma Interferon by Peripheral Mononuclear Cells in Human Schistosoma mansoni Infection Normalizes after Chemotherapy

“…In that study, exogenous lL-2 resulted in partial normalization of responses, an observation that was also made in a study of heavily S. »)a«.v(tH/-infected Sudanese children [17]. The conclusion that underproduction rather than in vitro binding of IL-2 occurs is supported by additional experimental data [34] and by our failure to detect any differences between controls and schislosomiasis patients when membrane IL-2 receptor (IL-2R) of PWM-stimulated PBMC was quantified by enzyme immunoassay (O. Alasevic-Josimovic and K. Zwingenberger. unpublished observation).…”

In vivoregulation ofS. japonicagranuloma formation by an IL-2 antagonist

“…Recent studies (Stavitsky & Harold 1988Stavitsky, 1987) have shown a temporal coincidence in the reduction in SEA-induced IL-2 production of spleen cells, hepatic granulomas and cells isolated from the granulomas, with the spontaneous modulation of SEA-induced hepatic granuloma formation. In these studies, a causal relationship is suggested between the reduced IL-2 production and reduced hepatic granulomatous inflammation.…”

“…Several studies have recently focused on T cell autocrines including interleukin-2 (IL-2) (Stavitsky & Harold, 1988Mathew & Boros, 1986;Secor, Stewart & Colley, 1990) and their activity and production during the course of schistosome infection. In Nippostrongylus brasiliensis infection and schistosomiasis, antibody to IL-5 has been shown to inhibit helminth-induced eosinophilia (Sher et al 1990;Coffman et al 1989).…”