Schistosoma mansoni PIII antigen modulates in vitro granuloma formation by regulating CD28, CTLA-4, and CD86 expression in humans.
We investigated the in vitro responses of peripheral blood mononuclear cells (PBMC) from intestinal chronic schistosomiasis patients to PIII, a multivalent antigen prepared from Schistosoma mansoni adult worm. PIII decreased cellular proliferation and granulomatous reaction. Moreover, induced the reduction of IFN-gamma levels and increased IL-10 production. To better understand the mechanism through which the observed suppression occurs, the present study focused on the phenotypic pattern displayed by PBMC treated with PIII in an in vitro granuloma assay. Expression of the surface markers CD28, CTLA-4 and CD86 by lymphocytes and monocytes were analyzed by flow cytometry. Our results demonstrated a significant decrease of CD28+CD4+ and CD28+CD8+ T-cell percentage stimulated by PIII compared to its non-infected counterparts. This suppressive effect was related to a significant increase in the percentage of T-cells expressing CTLA-4. PIII also promoted a significant increase in the percentage of cells expressing CD86. Indeed, our results demonstrated that PIII was capable of modulating in vitro granuloma reaction, and this event was related to the balance of IL-10, IFN-gamma and CD28, CTLA-4, CD86 bringing new insight to the immunoregulation of granulomatous hypersensitivity in human schistosomiasis.
Zouain
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CS
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Caixa Postal 486, CEP 31.270-901, Belo Horizonte, Brazil.
Falcão
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Goes
T S
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Leite
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MF
Goes
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D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D000947:Antigens, Helminth / Q000276:immunology / Q000378:metabolism*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006099:Granuloma / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000469:parasitology; D008214:Lymphocytes / Q000378:metabolism / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000469:parasitology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000947:Antigens, Helminth; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D008562:Membrane Glycoproteins