title: The combined effect of IL-4 and IL-10 suppresses the generation of, but does not change the polarity of, type-1 T cells in Histoplasma infection.
abstract: Dominant type-1 cytokine production is induced in a murine model of systemic histoplasmosis. We used this model to investigate whether the presence of antagonistic cytokines during T cell priming changes the polarity of T cells in response to Histoplasma infection. Before infection with Histoplasma capsulatum, mice were injected twice with goat anti-mouse IgD antiserum (GalphaMdelta), which induced expression of dominant type-2 cytokines. At days 7 and 14 after infection, the GalphaMdelta-treated mice had suppressed IFN-gamma response and a significantly greater fungal burden in their spleens and lungs. The number of IFN-gamma-producing cells as well as the level of IFN-gamma produced per cell was greatly reduced. Not only CD4+ T cells but also CD8+ T cells were affected. The number of Histoplasma-induced IFN-gamma-producing cells was partially restored in GalphaMdelta-treated IL-4-/- and IL-10-/- mice and completely restored in IL-4-/- IL-10-/- mice. Thus, the combined effect of IL-4 and IL-10 suppressed the generation of IFN-gamma-producing cells. A longitudinal study demonstrated that as IL-4 and IL-10 decreased, the number of Histoplasma-induced IFN-gamma-producing cells rapidly increased, and fungal clearance improved, demonstrating that the presence of IL-4 and IL-10 did not permanently change the polarity of T cells.
authors.affiliation: Graduate Institute of Immunology, College of Medicine, National Taiwan University, No. 1 Jen-Ai Road, Section 1, Taipei 100, Taiwan, Republic of China.
authors.forename: Jung-Kuei
authors.initials: JK
authors.lastname: Peng
authors.forename: Jr-Shiuan
authors.initials: JS
authors.lastname: Lin
authors.forename: John T
authors.initials: JT
authors.lastname: Kung
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: Betty A
authors.initials: BA
authors.lastname: Wu-Hsieh
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D006658:Histoplasma; D006660:Histoplasmosis / Q000276:immunology*; D007106:Immune Sera / Q000494:pharmacology; D007072:Immunoglobulin D / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D007106:Immune Sera; D007072:Immunoglobulin D; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma