title: IL-12-assisted immunization generates CD4+ T cell-mediated immunity to Listeria monocytogenes.
abstract: Mice infected with virulent Listeria monocytogenes develop long-lived acquired immunity. We previously reported that acquired immunity to Listeria could also be elicited by immunizing mice with non-viable Listeria or listerial proteins/peptides in combination with IL-12. Here we show that this IL-12-assisted immunization strategy was effective in class I but not in class II MHC-deficient mice, suggesting that antigen-specific CD4(+) T cells are selectively generated using this adjuvant system. We have also evaluated the importance of endogenous production of IFN-gamma and IL-12 for the efficacy of IL-12-assisted immunization. IFN-gamma-deficient mice immunized with HKLM and IL-12 failed to produce effective Listeria-specific responses. In contrast, IL-12-deficient mice were able to generate protective antigen-specific T cell responses in response to immunization with HKLM and IL-12, indicating that exogenous IL-12 is sufficient to initiate a cytokine cascade that results in a potent T(H)1 response. IL-12-assisted immunization provides a model in which both the generation and effector mechanisms of anti-bacterial antigen-specific CD4(+) effector cells can be analyzed.
authors.affiliation: Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Avenue, Molecular Sciences Building, Room 701F, Memphis, TN 38163, USA. mamiller@utmem.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Miller
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Skeen
authors.forename: Christy L
authors.initials: CL
authors.lastname: Lavine
authors.forename: H
authors.initials: H
authors.lastname: Kirk Ziegler
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000276:Adjuvants, Immunologic; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma