Cytokine Control of Parasite-Specific Anergy in Human Urinary Schistosomiasis

Abstract

Humans chronically infected with schistosomiasis usually have impaired parasite Ag-specific lymphocyte proliferation and IFN-y 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. 11-10 has been shown to exert an inhibitory effect on cell-mediated immunity. To determine whether endogenous 11-10 has a role in regulating parasite-specific anergy in schistosomiasis, neutralizing anti-11-10 added to PBMC from Schistosoma haematobium patients' enhanced adult worm (SWAP)or egg Ag (SEA)-driven lymphocyte proliferation and/or IFN-y production by 2to >lOO-fold in 32 of 38 subjects. In contrast, anti-11-10 failed to significantly augment the mycobacterial Ag, purified protein derivative (PPD)-driven lymphocyte proliferation, or IFN-.)I production in 9 or 10 of 14 individuals, respectively. SWAP or SEA triggered 11-10 release from PBMC of both patients and healthy individuals; however, CD4+ cells were a significant source of 11-10 only in infected subjects. PPD relative to SWAP induced fivefold less 11-10 release by CD4+ cells ( p < 0.01). A possible mechanism whereby 11-1 0 suppressed Ag-specific T cell responses was demonstrated by the ability of SWAP and not PPD to suppress B7 expression on PBMC. Anti-11-10 completely inhibited the parasite Ag-induced down-regulation of 87 expression. These studies indicate that 11-10 contributes to parasite Ag-induced T cell hyporesponsiveness observed in patients with chronic schistosomiasis hematobia. The Iournal of Immunology, 1996, 156: 471 5-4721.