CD4+ T cells are required during priming but not the effector phase of antibody-mediated IFN-gamma-dependent protective immunity against pulmonary Francisella novicida infection

Immunol Cell Biol. Aug-Sep 2008;86(6):515-22. doi: 10.1038/icb.2008.31. Epub 2008 Apr 22.

Abstract

We have previously demonstrated the protective efficacy of intranasal vaccination with a defined Francisella tularensis subsp. novicida DeltaiglC mutant (KKF24) against pulmonary F. novicida U112 challenge. In this study, we further characterized the mechanisms of KKF24-induced immunity. Intranasally vaccinated KKF24 C57BL/6 major histocompatibility class (MHC) class II-/- mice produced minimal antigen-specific interferon (IFN)-gamma and serum antibodies and were highly susceptible (0% survival) to F. novicida challenge, compared to MHC class I-/- or wild-type mice (both 100% survival). Protective immunity could be transferred by immune serum into recipient wild type, but not IFN-gamma-/- mice. The protective effect of KKF24 vaccination against the respiratory F. novicida U112 challenge was not abrogated by anti-CD4 neutralizing antibody treatment and was not conferred by adoptive transfer of KKF24-specific CD4+ T cells. The protective effect of antibody was partially dependent upon Fc receptor-mediated clearance. Taken together, our data indicate that CD4+ T cells are required for priming, but not during the effector phase, of anti-KKF24 antibody-mediated IFN-gamma-dependent immunity against pulmonary F. novicida infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Bacterial / physiology*
  • Bacterial Vaccines / administration & dosage*
  • Bacterial Vaccines / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Francisella tularensis / genetics
  • Francisella tularensis / immunology
  • Genes, MHC Class I / physiology
  • Genes, MHC Class II / physiology
  • Immunity, Cellular
  • Immunization
  • Interferon-gamma / immunology*
  • Lung / microbiology*
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, IgG / physiology
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Survival Rate
  • Tularemia / immunology*
  • Tularemia / prevention & control*
  • Vaccination

Substances

  • Antibodies, Bacterial
  • Bacterial Vaccines
  • Fcgr1 protein, mouse
  • Fcgr3 protein, mouse
  • Receptors, IgG
  • Interferon-gamma