Evidence of a T helper type 2 activation in human schistosomiasis

Abstract

The lymphocyte proliferative response and cytokine production to S. mansoni antigen in vitro were evaluated in 22 schistosomiasis patients living in an area endemic for this disease. The majority of patients (86%) showed no lymphocyte proliferative response and none of them showed interferon-gamma (IFN-gamma) production, following in vitro stimulation with soluble adult worm antigen preparation (SWAP). In contrast, interleukin (IL)-5 (2038 +/- 1757 pg/ml) and IL-10 (867 +/- 762 pg/ml) were detected in peripheral blood mononuclear cell (PBMC) cultures stimulated with SWAP. Moreover, mRNA for IL-4 was detected in SWAP-stimulated PBMC from 4 of 6 patients evaluated. Restoration of lymphoproliferative response was achieved in 4 of 6 patients by adding anti-IL-10 monoclonal antibody (mAb) to PBMC cultures [mean stimulation index (SI) in the presence of antigen = 2.7 +/- 2.9; SI in the presence of antigen plus anti-IL-10, 21 +/- 16]. Restoration of IFN-gamma production by addition of anti-IL-10 mAb was achieved in 4 of 12 patients evaluated (248, 350, 687 and 710 pg/ml). Moreover, the addition of IL-10 to PBMC cultures of 3 schistosomiasis patients and 2 cured subjects who had high lymphoproliferative responses to SWAP resulted in the suppression of these responses by 90%, and completely suppressed IFN-gamma production in one of the subjects, whose PBMC produced IFN-gamma after stimulation with SWAP. The presence of IL-4 mRNA, high levels of IL-5, and the absence of IFN-gamma in PBMC culture supernatants from infected patients, supports the conclusion that patients living in an endemic area of schistosomiasis express a predominant T helper type 2 response. The high levels of IL-10 and the ability of neutralizing anti-IL-10 mAb to restore T cell responses indicate that this cytokine plays an important role in the modulation of T cell responses in schistosomiasis.

Cytokine Regulation of Human Immune Response to Schistosoma mansoni: Analysis of the Role of IL‐4, IL‐5 and IL‐10 on Peripheral Blood Mononuclear Cell Responses

“…We have also demonstrated that addition of recombinant IL-10 to cultures can down-modulate the PBMC response of all schistosome-infected patients, suggesting that although the cells from acute or HS patients do not secrete IL-10, they are able to respond to the recombinant cytokine. The involvement of IL-10 in modulating the proliferative response of PBMC from INT during schistosomiasis mansoni or schistosomiasis hematobia has been reported previously [35,36]. It has been demonstrated that the lymphoproliferative response of PBMC from INT patients to SWAP could be restored by adding anti-IL-10 monoclonal antibodies.…”

Schistosoma mansoni antigen-driven interleukin-10 production in infected asthmatic individuals

“…IL-10 is an anti-inflammatory cytokine produced by a variety of cells such as macrophages, T CD4 + , T CD8 + and T CD4 + CD25 + cells. While in the chronic phase of S. mansoni infection IL-10 is produced in high levels (Gazzinelli & Colley 1992, Williams et al 1994, Araujo et al 1996, in asthma, despite the immune response being the Th2 type, the production of IL-10 is impaired. Studies have shown that IL-10 is protective against asthma, and increases in levels during immunotherapy (Akdis et al 1998).…”

Neuroschistosomiasis due to Schistosoma mansoni: a review of pathogenesis, clinical syndromes and diagnostic approaches

“…Granuloma formation can occur in environments dominated by either Th-1 or Th-2 type cytokines 39 . Th-1 cytokine profile has been preferentially associated with hepato-splenic schistosomiasis 34 whereas patients with intestinal disease present elevated anti-inflammatory Th-2-type cytokine 4 . The immune response to the antigens released from the ova is at a maximum intensity in the early stages of infection, leading to the formation of necrotic-exudative granulomas and the immune response declines over the course of the infection 9 .…”