IL-10 mediates immunosuppression following primary infection with Toxoplasma gondii in mice.
Suppression of the host immune response by Toxoplasma gondii has been observed in both human and experimental murine infection. In this study, inbred mice were infected with T. gondii. At day 7 post-infection, the lymphoproliferative response to both mitogen and superantigen as well as parasite antigen were found to be significantly depressed. Using a transwell system, it was determined that the reduced proliferative response was due to soluble factor(s) being expressed by splenocytes from the infected mice. Isolation of the splenocytes into an adherent and nonadherent population suggested that both macrophages and T cells were able to produce at least one soluble factor. Tissue culture supernatant derived from the splenocytes of the infected mice contain increased levels of IL-10, whereas measurable IL-2 levels could not be quantitated. At day 7 post-infection, both a biologic assay for IFN-gamma in culture supernatant and the expression of IFN-gamma mRNA in the splenocytes were reduced. Antibody to IL-10 was able to partially neutralize (almost 50%) the in vitro immune downregulation of the tissue culture supernatant. Anti-IL-10 in combination with a nitric oxide (NO) antagonist was able to reverse the inhibitory activity of the culture supernatant by 85%. Since IL-10 is a potent antagonist of IFN-gamma, it may represent a critical cytokine involved in mediating T. gondii induced immunosuppression in the infected host.
Khan
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IA
Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Matsuura
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T
Kasper
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LH
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008934:Mitogens / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000166:cytology; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D000906:Antibodies; D000953:Antigens, Protozoan; D016207:Cytokines; D008934:Mitogens; D012333:RNA, Messenger; D018089:Superantigens; D016753:Interleukin-10; D009569:Nitric Oxide