CYTOKINE CONTROL OF PARASITE-SPECIFIC ANERGY IN HUMAN URINARY SCHISTOSOMIASIS - IL-10 MODULATES LYMPHOCYTE-REACTIVITY

Humans chronically infected with schistosomiasis usually have impaired parasite Ag-specific lymphocyte proliferation and IFN-gamma productio n that may facilitate persistence of the parasite while producing litt le 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 det ermine whether endogenous IL-10 has a role in regulating parasite-spec ific 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 producti on by 2- to >100-fold in 32 of 38 subjects. In contrast, anti-IL-10 fa iled to significantly augment the mycobacterial Ag, purified protein d erivative (PPD)-driven lymphocyte proliferation, or IFN-gamma producti on in 9 or 10 of 14 individuals, respectively. SWAP or SEA triggered I L-10 release from PBMC of both patients and healthy individuals; howev er, CD4(+) cells were a significant source of IL-10 only in infected s ubjects, PPD relative to SWAP induced fivefold less IL-10 release by C D4(+) cells (p < 0.01). A possible mechanism whereby IL-10 suppressed Ag-specific T cell responses was demonstrated by the ability of SWAP a nd not PPD to suppress B7 expression on PBMC, Anti-IL-10 completely in hibited the parasite Ag-induced down-regulation of B7 expression. Thes e studies indicate that IL-10 contributes to parasite Ag-induced T cel l hyporesponsiveness observed in patients with chronic schistosomiasis hematobia.