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

C L King, A Medhat, I Malhotra, M Nafeh, A Helmy, J Khaudary, S Ibrahim, M El-Sherbiny, S Zaky, R J Stupi, K Brustoski, M Shehata (+1 others)
1996 Journal of Immunology  
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
more » ... y 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.
doi:10.4049/jimmunol.156.12.4715 fatcat:bcebojkihnhwhcp4xvc6epthky