Immunosuppressive components of Ascaris suum down-regulate expression of costimulatory molecules and function of antigen-presenting cells via an IL-10-mediated mechanism.
High-molecular-weight components (PI) of Ascaris suum suppress both cell-mediated and humoral responses against ovalbumin (OVA) via an IL-4/IL-10-dependent mechanism. The aim of this work was to investigate the effect of PI on the ability of APC to activate T cells and the role of IL-10 in this process. Flow cytometry analyses of MHC class II, CD80, CD86 and CD40 molecules on LN cells from mice immunized with OVA or OVA+PI showed that PI inhibits expression of these molecules on unfractionated cells and on purified CD11c(+) cells. A low proliferative response was obtained when OVA-specific TCR-Tg T cells were incubated with CD11c(+) cells from OVA+PI-immunized mice pulsed with OVA, when compared to those incubated with cells from OVA-immunized mice. Similar results were obtained using as APC CD11c(+) cells from OVA-immunized mice pulsed with OVA+PI, which also expressed less of the four markers. The inhibitory effect of PI on both the expression of costimulatory molecules and the induction of T cell proliferation was abolished in IL-10-deficient mice. Our data indicate that the potent immunosuppressive effect of A. suum extract components on the host immune system is primarily related to their property of down-regulating the Ag-presenting ability of DC via an IL-10-mediated mechanism.
Silva
Sandriana R
SR
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Jacysyn
Jacqueline F
JF
Macedo
Mahasti S
MS
Faquim-Mauro
Eliana L
EL
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D017165:Ascaris suum / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000276:immunology; D019013:CD40 Antigens / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10