Down modulation of MHC surface molecules on B cells by suppressive immune complexes obtained from chronic intestinal schistosomiasis patients

doi:10.1016/S0165-2478(98)00026-1

Immunology Letters

Volume 62, Issue 2, June 1998, Pages 67-73

https://doi.org/10.1016/S0165-2478(98)00026-1 Get rights and content

Abstract

Granulomatous inflammation around parasite eggs is the prominent lesion in human schistosomiasis. Studies have suggested the involvement of a series of suppressive mechanisms in the control of this reaction, such as macrophages, cytokines, idiotipic interactions and immune complexes (IC). The studies examine the role of IC obtained from chronic intestinal schistosomiasis patients (ISP) in the reactivity of peripheral blood mononuclear cells (PBMC). The results have shown that these immune complexes are able to suppress cell reactivity by inducing an increase in the production of soluble mediators such as prostaglandins and IL-10. To gain a better understanding of how this suppression occurs the present study examines the phenotypic pattern of PBMC after immune complex treatment in cell proliferation assays. These data show that cultures including immune complex present a higher percentage of B lymphocytes in which a lower expression of a MHC-class II gene product, HLA-DR was detected. This altered expression of the HLA-DR molecule on B lymphocytes after IC treatment suggests a novel mechanism for the suppression observed, that is, IC might decrease the antigen-presenting function of B lymphocytes.

Introduction

Human schistosomiasis is a chronic infection that is caused in the overwhelming majority of cases by one of three species of parasitic helminths: (1) Schistosoma mansoni; (2) S. haematobium; or (3) S. japonicum [1]. The granulomatous lesions in the liver, which consist mostly of eosinophils, macrophages, fibroblasts and lymphocytes, constitute a primary pathological feature of schistosomiasis. These granulomas can evolve into fibrous scars and eventually contribute to widespread fibrosis, portal hypertension and varicocele formation [2]. The development of severe pathology is related to the intensity of infection and it appears to result from an inappropriate host immune response to egg Ag. However, in most patients the immune system develops a series of immunomodulatory processes and a discrete response to egg antigens is observed. These processes have been studied in human schistosomiasis by evaluations of in vitro cell reactivity including cell proliferation and granuloma formation assays 3, 4, 5.

In this context, it has been shown that IC isolated from sera of chronic intestinal schistosomiasis patients (ISP) can have an inhibitory effect on in vitro granuloma reaction and cell proliferation to S. mansoni antigens 5, 6, 7, 8. The studies have shown the involvement of soluble mediators such as prostaglandin E series [7]and IL-10 in these mechanisms, accompanied by a decrease in TNF-α an important cytokine involved in granuloma formation [8]. In order to better understand the role played by IC in the suppression of cell reactivity, additional studies concerning the phenotypic characterization of PBMC obtained from schistosomiasis patients were developed. These studies aimed to analyse the influence of IC on the cell phenotype and the expression of costimulatory molecules involved in the reactivity of these cells. No difference was detected in the expression of T lymphocytes and of their subpopulations CD4⁺ and CD8^bright T cells from IC-treated cultures when compared to non-treated cultures. The expression of CD28, a costimulatory molecule involved in the activation of T lymphocytes, was also the same on non-treated and IC-treated cells. Interestingly, a higher percentage of B lymphocytes in IC-treated PBMC were detected but a lower expression of HLA-DR by these cells. This altered expression of HLA-DR on B lymphocytes after IC treatment suggests one of the mechanisms for the suppression observed is through the decrease of the antigen-presenting function of B lymphocytes.

Section snippets

Study population

Chronic intestinal schistosomiasis patients (ISP) were selected based on clinical and parasitological stool examination for the presence of S. mansoni eggs in Fundação Nacional da Saúde, Santa Luzia, MG, Brazil. The patient protocols used throughout this study were approved by the human subject ethics committee in Brazil.

Isolation of IC

The ISP sera diluted 1/8 were precipitated by using polyethylene glycol 6000 (PEG, Sigma P-2139) at a final concentration of 4%. This mixture was incubated overnight at 4°C,

Effect of immune complexes on cell reactivity

In this assay the effect of IC on the proliferative response of PBMC obtained from ISP to SEA and SWAP was tested (Table 1). A total of ten of 12 patients analyzed reacted to SEA, while all of them reacted to SWAP. The response to SWAP was significantly greater than the response to SEA. As observed previously, IC from ISP induced a marked suppression of cell proliferation to SEA and SWAP (P<0.05). The suppressive effect of IC on the proliferative response of PBMC varied from 20 to 71% in cells

Discussion

Severe schistosomiasis is a disease characterized by hepatic and intestinal granuloma formation around parasite eggs deposited within the hepatic presinusoidal spaces and the gut. These granulomas constitute the primary pathological feature of schistosomiasis and, in the chronic phase, regulation of this lesion occurs, resulting in smaller anti-egg granulomas [2]. Recent studies have demonstrated that several immunoregulatory mechanisms may be operating in human schistosomiasis. The possible

Acknowledgements

This investigation received financial assistance from CNPq, FINEP, (PRONEX-SCH2), PRPq/UFMG, FAPEMIG and NIH: Grant AI 26 505.

References (15)

E.J Pearce et al.
D.G Colley
P.O Flores-Villanueva et al.
J. Immunol.
(1996)
M.A Montesano et al.
J. Immunol.
(1989)
A.M Goes et al.
Am. J. Trop. Med. Hyg.
(1991)
A.M Goes et al.
Parasite Immunol.
(1994)
S.A Rezende et al.
Braz. J. Med. Biol. Res.
(1993)

There are more references available in the full text version of this article.

Cited by (7)

Identification and characterization of immune complexes in the cerebrospinal fluid of patients with spinal cord schistosomiasis
2011, Journal of Neuroimmunology
Citation Excerpt :
The possible role of these ICs in the pathogenesis of SCS remains unknown. They may be involved in the genesis of the immune-mediated vascular lesions and/or in the down-modulation of granuloma formation as was demonstrated in other clinical forms of schistosomiasis mansoni (Goes et al., 1991; Rezende et al., 1993; Rezende et al., 1998). In the acute phase of this infection, there is evidence that ICs and pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) are responsible for the genesis of the symptoms of the toxemic form (Hiatt et al., 1980; de Jesus et al., 2002).
The pathogenesis of neuroschistosomiasis is largely unknown. Available evidence suggests that it depends on the presence of parasite eggs in the nervous tissue and on the host's immune response. We investigated the presence of immune complexes (ICs) in the cerebrospinal fluid (CSF) of four patients with spinal cord schistosomiasis (SCS), and performed their characterization. ICs containing soluble egg antigen of Schistosoma mansoni (SEA) were found in the CSF of all the SCS patients. To our knowledge, this is the first evidence of ICs containing schistosomal antigens in the CSF of patients with SCS. Further studies are necessary to confirm our findings and investigate the possible roles of ICs in the pathogenesis of this disease.
Human immune response in schistosomiasis: The role of P24 in the modulation of cellular reactivity to Schistosoma mansoni antigens
2002, Human Immunology
Schistosome antigenic components are being tested as vaccine candidates with various degrees of success, but there are only few reports using multivalent antigens to stimulate an appropriate immune response that leads to resistance or granuloma modulation. We investigated the in vitro response of peripheral blood mononuclear cells (PBMC) from chronic intestinal schistosomiasis individuals to PIII, a multivalent antigen prepared from Schistosoma mansoni adult worm antigen, and response to P24, a single antigen obtained from PIII. Treatment of PBMC with either PIII or P24 caused significant decrease in cellular proliferation and granuloma formation induced by S. mansoni antigens, and a significant elevation in IL-10 and TNF-α but not in IFN-γ production. Moreover, P24 promoted an elevation in TNF-α level on the in vitro granuloma reaction, when cocultured with polyacrylamide beads (PB) coupled to S. mansoni antigens. These findings suggest that, besides inducing protective immunity, PIII and P24 antigens seem to be important in the regulation of in vitro granuloma formation through stimulation of IL-10 and TNF-α production in human schistosomiasis. The more pronounced effect of P24 on reducing the in vitro granulomatous reaction could be associated with a balance between IL-10 and TNF-α production.
The role of IL-10 and IgG1 in the protection and granulomatous response in Schistosoma mansoni P24-immunized mice
2000, Vaccine
Previous work by our laboratory identified a fraction of Schistosoma mansoni soluble adult worm antigenic preparation, designated PIII, able to elicit significant in vitro cell proliferation, and lower in vitro and in vivo granuloma formation. In the present work, we investigated some biological activities of P24, an antigenic component of PIII. Immunization of mice with this antigen induced a significant protection degree against challenge infection and significant decrease in the hepatic granuloma formation. Pre-incubation of spleen cells from P24-immunized mice with S. mansoni antigens induced a significant increase of interleukin (IL)-10 levels, but not interferon-γ, in the cell supernatants. In addition, mice immunized with different S. mansoni antigens and P24 displayed indistinguishable levels of IgG2a in response to anti-S. mansoni antigens, while IgG1 levels were significantly increased. Collectively, our results indicate that P24 might mediate protective anti-parasite immunity and downregulate granulomatous hypersensitivity to S. mansoni eggs in part by its ability to induce a higher production of IgG1 and IL-10.
Chronic schistosome infection leads to modulation of granuloma formation and systemic immune suppression
2013, Frontiers in Immunology
Aberrant receptor-mediated endocytosis of Schistosoma mansoni glycoproteins on host lipoproteins
2006, PLoS Medicine
Regulation of Granulomatous Inflammation in Experimental Models of Schistosomiasis
2004, Infection and Immunity

View all citing articles on Scopus

View full text