Cytokine control of parasite-specific anergy in human urinary schistosomiasis. IL-10 modulates lymphocyte reactivity.

Abstract

Humans chronically infected with schistosomiasis usually have impaired parasite Ag-specific lymphocyte proliferation and IFN-gamma production that may facilitate persistence of the parasite while producing little clinical disease. The mechanisms that contribute to the immunologic hyporesponsiveness in these patients remain undefined. IL-10 has been shown to exert an inhibitory effect on cell-mediated immunity. To determine whether endogenous IL-10 has a role in regulating parasite-specific anergy in schistosomiasis, neutralizing anti-IL-10 added to PBMC from Schistosoma haematobium patients' enhanced adult worm (SWAP)- or egg Ag (SEA)-driven lymphocyte proliferation and/or IFN-gamma production by 2- to >100-fold in 32 of 38 subjects. In contrast, anti-IL-10 failed to significantly augment the mycobacterial Ag, purified protein derivative (PPD)-driven lymphocyte proliferation, or IFN-gamma production in 9 or 10 of 14 individuals, respectively. SWAP or SEA triggered IL-10 release from PBMC of both patients and healthy individuals; however, CD4+ cells were a significant source of IL-10 only in infected subjects. PPD relative to SWAP induced fivefold less IL-10 release by CD4+ cells (p < 0.01). A possible mechanism whereby IL-10 suppressed Ag-specific T cell responses was demonstrated by the ability of SWAP and not PPD to suppress B7 expression on PBMC. Anti-IL-10 completely inhibited the parasite Ag-induced down-regulation of B7 expression. These studies indicate that IL-10 contributes to parasite Ag-induced T cell hyporesponsiveness observed in patients with chronic schistosomiasis hematobia.

Schistosoma mansoni infection is associated with a reduced course of asthma

“…19 Although it is not clear how helminths decrease SPT response to aeroallergens, it has been speculated that the high levels of IgE, mast cell Fc RI blockage by polyclonal IgE, high concentrations of antigen-specific IgG 4 , or downregulation of mite-specific IgE production might participate in this phenomenon. [20][21][22][23][24] Our findings argue against the hypothesis that high levels of polyclonal IgE antibodies reduce SPT reactivity in helminth-infected subjects 9 because we did not find a difference in the levels of total IgE antibodies among the groups. Previous studies have shown that infection with S mansoni, S haematobium, and A lumbricoides decreases the skin test response to indoor allergens.…”

IL-10 Regulates Liver Pathology in Acute MurineSchistosomiasis mansoniBut Is Not Required for Immune Down-Modulation of Chronic Disease

“…The switch from Th1 to Th2 cytokine dominance coincides with patency and has been attributed to the development of an immune response to the eggs that are first produced by the adult female parasites between 4 and 5 wk postinfection. In vitro studies have suggested that IL-10 is in large part responsible for the suppression of IFN-␥ expression in infected mice (15), a finding that has also been observed with PBMC obtained from infected humans (30). One hypothesis is that the early Th1-type response is an essential component of the acute granulomatous response and that immunomodulation occurs as a result of the down-regulation of the Th1 response (11).…”