title: Endogenous IL-12 synthesis is not required to prevent hyperexpression of type 2 cytokine and antibody responses.
abstract: Endogenous IL-12 production is hypothesized to play an essential role preventing spontaneous expression of type 2 responses, acting as a natural inhibitor limiting development of immediate hypersensitivity. Here, IL-12-deficient p35(- / -) and p40(- / -) mice were used to examine the role of endogenous IL-12 and p40 homodimer during in vivo development of exogenous antigen-driven responses. In the absence of deliberate immunization, IL-12-deficient mice exhibited greatly reduced serum IgG2a but IgG1 / IgE levels no higher than controls. Immunization to elicit polarized ovalbumin-specific type 1 or type 2 dominant responses, or using Trichinella spiralis extract in the absence of adjuvants, led to IFN-gamma production of approximately 10 % of C57BL / 6 controls yet the kinetics and intensity of primary and secondary type 2 cytokine (IL-4, IL-5, IL-13) and antibody (IgG1, IgE) responses, as well as functional IL-12 receptor expression, were consistently unaltered. Thus, while IL-12 provides an important positive signal for Th1 development, antigen exposure in its absence does not lead to generalized enhancement of type 2 cytokine or antibody responses. The data argue that endogenous IL-12 production is not required as a constitutive negative regulator limiting induction or expression of type 2 effector responses.
authors.affiliation: Department of Immunology, University of Manitoba, Winnipeg, Canada.
authors.forename: J D
authors.initials: JD
authors.lastname: Rempel
authors.forename: I P
authors.initials: IP
authors.lastname: Lewkowich
authors.forename: K T
authors.initials: KT
authors.lastname: HayGlass
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma