IL-12-assisted immunization generates CD4 + T cell-mediated immunity to Listeria monocytogenes

• Published in: Cellular immunology Vol. 222; no. 1; pp. 1 - 14
• Main Authors: Miller, Mark A., Skeen, Marianne J., Lavine, Christy L., Kirk Ziegler, H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.03.2003
• Subjects: Adjuvant; Adjuvants, Immunologic - pharmacology; Animals; CD4-Positive T-Lymphocytes - immunology; Cytokine; Female; Histocompatibility Antigens Class I - physiology; Histocompatibility Antigens Class II - physiology; IL-12; Immunity; Immunization; Interferon-gamma - biosynthesis; Interleukin-12 - pharmacology; Interleukin-2 - biosynthesis; Listeria; Listeria monocytogenes - immunology; Male; Mice; Mice, Inbred C57BL; Vaccine; Immunization; Listeria; Cytokine; Vaccine; Adjuvant; IL-12; Immunity
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/S0008-8749(03)00083-2

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-γ and IL-12 for the efficacy of IL-12-assisted immunization. IFN-γ-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 H1 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.