title: IL-12 and IFN-gamma are required for initiating the protective Th1 response to pulmonary cryptococcosis in resistant C.B-17 mice.
abstract: A murine model was used to assess the role of cytokines in initiating protective T-cell-mediated immunity in the lung. A pulmonary infection was initiated by intratracheal inoculation of Cryptococcus neoformans (Cne). Previously, we had established that Cne lung clearance was mouse-strain-specific: C.B-17 mice were resistant and developed a Th1-like response, whereas C57BL/6 mice were susceptible and did not develop a Th1 response. In the present study we showed that monoclonal anti-interferon-gamma (IFN-gamma) and anti-interleukin-12 (IL-12) antibody administration prior to infection of resistant C.B-17 mice inhibited lung clearance of Cne. Cytokine profiles of lung and lung-associated lymph nodes (LALN) from monoclonal antibody (mAb)-treated C.B-17 mice were switched from Th1-like to Th2-like, and mAb-treated C.B-17 mice exhibited lung eosinophilia, which was absent in control C.B-17 mice. Additionally, C.B-17 mice treated with anti-IFN-gamma and anti-IL-12 mAb demonstrated a significantly lower percentage of lung macrophages expressing inducible nitric oxide synthase (iNOS) than did control mice. These studies clearly demonstrate that both IFN-gamma and IL-12 are required for initiation of a Th1 response in resistant C.B-17 mice.
authors.affiliation: Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-8576, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Hoag
authors.forename: M F
authors.initials: MF
authors.lastname: Lipscomb
authors.forename: A A
authors.initials: AA
authors.lastname: Izzo
authors.forename: N E
authors.initials: NE
authors.lastname: Street
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003453:Cryptococcosis / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000302:isolation & purification; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008171:Lung Diseases / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009500:Neutralization Tests; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018664:Interleukin-12; D007371:Interferon-gamma