IL-12 and IFN-gamma are required for initiating the protective Th1 response to pulmonary cryptococcosis in resistant C.B-17 mice

Am J Respir Cell Mol Biol. 1997 Dec;17(6):733-9. doi: 10.1165/ajrcmb.17.6.2879.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Cryptococcosis / immunology*
  • Cryptococcus neoformans / isolation & purification
  • Disease Susceptibility / immunology
  • Female
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interferon-gamma / physiology*
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology
  • Interleukin-12 / physiology*
  • Lung Diseases / immunology*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neutralization Tests
  • Th1 Cells / immunology*


  • Antibodies, Monoclonal
  • Interleukin-12
  • Interferon-gamma